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BACKGROUND AND OBJECTIVE The Newborn Weight Tool (NEWT) can inform newborn feeding decisions and might reduce health care utilization by preventing excess weight loss. Clinical decision support (CDS) displaying NEWT might facilitate its use. Our study’s objective is to determine the effect of CDS displaying NEWT on feeding and health care utilization. METHODS At an hospital involved in NEWT development, we randomly assigned 2682 healthy infants born ≥36 weeks gestation in 2018–2019 either to CDS displaying NEWT with an electronic flag if most recent weight was ≥75th weight loss centile or to a control of usual care with NEWT accessed at clinician discretion. Our primary outcome was feeding type concordant with weight loss, defined as exclusive breastfeeding for those not flagged, exclusive breastfeeding or supplementation for those flagged once, and supplementation for those flagged more than once. Secondary outcomes included inpatient and outpatient utilization in the first 30 days. We used χ2 and Student’s t tests to compare intervention infants with control and to compare trial infants with those born in 2017. RESULTS Feeding was concordant with for 1854 (74.5%) trial infants and did not differ between randomized groups (P = .65); concordant feeding was higher for all trial infants than for infants born in 2017 (64.4%; P < .0005). Readmission occurred for 51 (3.8%) CDS infants and 45 (3.4%) control infants (P = .56). Among the 60% of trial infants with outpatient records available, there were 3.5 ± 1.7 visits with no differences between randomized groups (P = .10). CONCLUSIONS At an hospital involved in NEWT development, CDS displaying NEWT did not alter either feeding or health care utilization compared with discretionary NEWT access.

Background Intervention Nurses Start Infants Growing on Healthy Trajectories tested an early life responsive parenting (RP) intervention designed for obesity prevention. Body mass index z-score at age 3 years was lower for the RP group versus controls with a larger effect for girls than boys. We sought to determine if child sex was associated with differing maternal feeding practices and whether sex moderated intervention effects on feeding. Design/Methods Mothers (N = 279) completed the Infant Feeding Styles Questionnaire (IFSQ) at 28 weeks, the Structure and Control in Parent Feeding (SCPF) at 1, 2, and 3 years, and the Child Feeding Questionnaire (CFQ) at 3 years. Study aims were tested using 2-way analysis of variance and repeated measures. Results Mothers reported greater restriction (limiting food quantity) for boys at 28 weeks (IFSQ: 3.0 ± 1.1 vs 2.8 ± 1.0, P = .07) and across annual measurements from age 1 to 3 years (SCPF: P = .04). At age 3, the intervention group effect on restriction differed by sex (CFQ: P = .047) such that higher restriction was reported by RP group mothers of boys versus girls (3.4 ± 0.7 vs 3.0 ± 0.9, P = .002) with no control group sex difference (3.4 ± 0.8 vs 3.3 ± 0.9, P = .79). There were no sex differences or sex by intervention group interactions in other reported feeding practices at any assessment (ie, structure-based feeding, pressure). Conclusions Mothers of boys used more restrictive feeding through age 3. These findings may be partially explained by previously reported better self-soothing and self-regulation abilities of participating girls.

A narrative review of randomized, blinded, controlled studies assessing the antipyretic effect of ibuprofen versus acetaminophen or combined or alternating treatment in children was conducted.Searches of the PubMed and Embase literature databases were conducted to identify relevant articles. Selected articles were limited to studies published in English that investigated OTC oral tablet and syrup formulations of acetaminophen and ibuprofen; there were no publication date limits. Open-label studies, nonrandomized studies, and those evaluating intravenous or suppository formulations of acetaminophen or ibuprofen were excluded. Variations in designs, endpoints, methods, and patient populations precluded our ability to conduct a formal systematic review.At physician-directed dosing (acetaminophen 15 mg/kg vs ibuprofen 10 mg/kg), no significant differences in antipyretic effects from 0‒6 h and between 0‒6, ‒12, ‒24, or ‒48 h, with single or multiple-doses, respectively, were observed. Tolerability profiles at physician dosing were similar. In 14 over-the-counter dose comparisons (acetaminophen, 10-15 mg/kg; ibuprofen, 2.5-10 mg/kg), antipyresis favored ibuprofen in 6, was similar between groups in 7, and favored acetaminophen (15 mg/kg vs ibuprofen 5 mg/kg) in 1 comparison. Both medications were well tolerated. Efficacy favored combination over individual components in 3 of 4 studies; alternating use results were mixed. All combination or alternating treatments were well tolerated.Antipyretic effects of ibuprofen and acetaminophen are similar at physician-directed doses; ibuprofen may be modestly superior at over-the-counter doses.

Newborns with neonatal abstinence syndrome (NAS) display symptoms related to neurologic excitability and autonomic dysfunction that result in increased metabolic demands. These infants also exhibit feeding difficulties and/or hyperphagia. Because the effects of these symptoms and behaviors on growth are unknown, we sought to measure serial body composition measurements over the first 4 months in infants with NAS requiring pharmacologic treatment using air displacement plethysmography. Fourteen infants of singleton birth with appropriate-for-gestational-age (AGA) weight and a gestational age of ≥35 weeks and N = 5) requiring multidrug therapy for symptom control had lower mean fat percent (−1.2%, CI: −5.2–2.1), fat mass (−60 g, CI: −25–13), and fat-free mass (−270 g, CI: −610–80) across time compared to infants requiring monotherapy. We are the first to report how body composition measures change over time in a small group of patients with NAS. Infants with NAS were smaller and leaner in the first several weeks compared to previously reported body composition measurements in term infants, but grew similarly to their healthy counterparts by 16 weeks. Infants with more severe NAS may be at risk for abnormalities in longer term growth.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.

BACKGROUND AND OBJECTIVES The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention for first-time mothers improved firstborn infant sleep compared with controls. The goals of this analysis were to test intervention spillover effects on secondborn siblings and examine birth order differences in infant sleep. METHODS Secondborns (n = 117) of INSIGHT mothers were enrolled in an observational cohort, SIBSIGHT. The Brief Infant Sleep Questionnaire was collected at 3, 16, and 52 weeks. Generalized linear mixed models assessed differences among secondborns by firstborn randomization, as well as birth order differences at 16 and 52 weeks. RESULTS The RP group secondborns slept 42 minutes longer at night (95% confidence interval [95% CI]: 19–64) and 53 minutes longer total (95% CI: 17–90) than control secondborns. RP secondborns were more likely to self-soothe to sleep (odds ratio [OR] = 2.0, 95% CI: 1.1–3.7) and less likely to be fed back to sleep after waking (OR = 0.5, 95% CI: 0.3–0.9) than secondborns of control mothers. RP secondborns were more likely to have a bedtime ≤8 pm at 3 (OR = 2.9, 95% CI: 1.1–7.7) and 16 weeks (OR = 4.7, 95% CI: 2.0–11.0). Few differences in sleep parenting practices were observed when comparing siblings within families. Secondborns slept 37 minutes longer than firstborns at 16 weeks (CI: 7–67, P = .03). CONCLUSIONS The INSIGHT RP intervention for first-time mothers had a spillover effect to secondborns, positively impacting sleep duration and behaviors. Intervening with first-time mothers benefits both firstborns and subsequent children.

Firstborn children are more likely to have obesity than secondborns, which may partially be explained by differential use of food to soothe (FTS) infant distress, which has been inked to higher weight status.To test associations between the birth order and maternal FTS and whether differences in sibling temperament and body mass index (BMI) z-scores were associated differences in maternal FTS.Random effect models assessed associations between birth order and FTS. Linear regressions examined associations between differences in maternal FTS and sibling differences in temperament at 16 weeks and BMI z-scores at 1 year.Mothers (n = 117) used contextual-based FTS more with firstborns than secondborns (2.70 vs. 2.38, p 0.0001). Sibling differences in negative affect were associated with differences in maternal contextual-based (RTo promote healthy child weight, mothers should learn to respond to each child's temperament and use alternatives to FTS infant distress.

Objectives Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. Methods This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. Results From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. Conclusions There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.

IntroductionBehavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of intervention-covariate interactions. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups.Methods and analysisSystematic searches of Medline, Embase, CENTRAL, CINAHL, PsycInfo, and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2020 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis (PMA) will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index (BMI) z-score at age 24 +/- 6 months using World Health Organisation Growth Standards, and effect differences will be explored among pre-specified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events.Ethics and disseminationApproved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations, and media releases.RegistrationProspectively registered on PROSPERO: CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis will be the largest individual participant data (IPD) meta-analysis evaluating behavioural interventions for the prevention of early childhood obesity to date, and will provide the most reliable and precise estimates of early intervention effects to inform future decision-making.IPD meta-analysis methodology will enable unprecedented exploration of important individual and trial-level characteristics that may be associated with childhood obesity or that may be effect modifiers.The proposed innovative methodologies are feasible and have been successfully piloted by members of our group.It may not be possible to obtain IPD from all eligible trials; in this instance, aggregate data will be used where available, and sensitivity analyses will be conducted to assess inclusion bias.Outcome measures may be collected and reported differently across included trials, potentially increasing imprecision; however, we will harmonise available data where possible, and encourage those planning or conducting ongoing trials to collect common core outcomes following prospective meta-analysis methodology.

IntroductionLittle is known about how early (e.g., commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to 1) characterise early obesity prevention interventions in terms of target behaviours, delivery features, and behaviour change techniques (BCTs), 2) explore similarities and differences in BCTs used to target behaviours, and 3) explore effectiveness of intervention components in preventing childhood obesity.Methods and analysisAnnual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the TOPCHILD Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components.Ethics and disseminationThe study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study’s findings will be disseminated through peer-reviewed publications, conference presentations, and targeted communication with key stakeholders.DiscussionOur study will provide an in depth understanding of behavioural components and delivery features used in obesity prevention interventions starting antenatally or in the first 12 months after birth. Understanding common intervention approaches in a systematic way will provide much needed insight to advance the design of early obesity prevention interventions and provide the opportunity to undertake future quantitative predictive modelling.RegistrationPROSPERO registration no. CRD42020177408STRENGTHS AND LIMITATIONS OF THIS STUDYThis study provides an understanding of behaviours targeted, behaviour change techniques and delivery features used in early childhood obesity prevention trials identified in a systematic review as being eligible for inclusion in the Transforming Obesity Prevention in CHILDren (TOPCHILD) Collaboration.Extends previous methods by coding behaviour change techniques in published and unpublished intervention materials and performing cross validation with trialists through the TOPCHILD Collaboration.Using standardised coding taxonomies will allow for comparisons across studies, and we will pilot test new ontologies from the Human Behaviour Change Project.Explores the complex area of targeting parent and caregivers’ behaviours to impact child outcomes across four key obesity prevention behavioural domains (relating to infant feeding practices, food provision and parent feeding practices, movement practices, sleep health practices).This study will provide preliminary results regarding the examination of intervention components’ effectiveness based on exploratory analysis. Yet, the internationally unique database this project creates will further our understanding of effective intervention components in future research.To date we already have 38 out of 65 eligible trials agreeing to share data, since not all trials may provide unpublished material we may perform sensitivity analyses comparing trials that have shared data to trials that have not shared materials.

Background Metabolomic analysis is commonly used to understand the biological underpinning of diseases such as obesity. However, our knowledge of gut metabolites related to weight outcomes in young children is currently limited. Objectives To (1) explore the relationships between metabolites and child weight outcomes, (2) determine the potential effect of covariates (e.g., child's diet, maternal health/habits during pregnancy, etc.) in the relationship between metabolites and child weight outcomes, and (3) explore the relationship between selected gut metabolites and gut microbiota abundance. Methods Using 1 H-NMR, we quantified 30 metabolites from stool samples of 170 two-year-old children. To identify metabolites and covariates associated with children's weight outcomes (BMI [weight/height2 ], BMI z-score [BMI adjusted for age and sex], and growth index [weight/height]), we analysed the 1 H-NMR data, along with 20 covariates recorded on children and mothers, using LASSO and best subset selection regression techniques. Previously characterized microbiota community information from the same stool samples was used to determine associations between selected gut metabolites and gut microbiota. Results At age 2 years, stool butyrate concentration had a significant positive association with child BMI (p-value = 3.58 × 10-4 ), BMI z-score (p-value = 3.47 × 10-4 ), and growth index (p-value = 7.73 × 10-4 ). Covariates such as maternal smoking during pregnancy are important to consider. Butyrate concentration was positively associated with the abundance of the bacterial genus Faecalibacterium (p-value = 9.61 × 10-3 ). Conclusions Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.

Significance Mitochondria frequently carry different DNA—a state called heteroplasmy. Heteroplasmic mutations can cause mitochondrial diseases and are involved in cancer and aging, but they are also common in healthy people. Here, we study heteroplasmy in 96 multigenerational healthy families. We show that mothers effectively transmit very few mitochondrial DNA to their offspring. Because of this bottleneck, which intensifies with increasing maternal age at childbirth, mutation frequencies can change dramatically between a mother and her child. Thus, a child might inherit a disease-causing mutation at high frequency from an asymptomatic carrier mother and might develop a disease. We also demonstrate that natural selection acts against disease-causing mutations during germline development. Our study has important implications for genetic counseling of mitochondrial diseases., Heteroplasmy—the presence of multiple mitochondrial DNA (mtDNA) haplotypes in an individual—can lead to numerous mitochondrial diseases. The presentation of such diseases depends on the frequency of the heteroplasmic variant in tissues, which, in turn, depends on the dynamics of mtDNA transmissions during germline and somatic development. Thus, understanding and predicting these dynamics between generations and within individuals is medically relevant. Here, we study patterns of heteroplasmy in 2 tissues from each of 345 humans in 96 multigenerational families, each with, at least, 2 siblings (a total of 249 mother–child transmissions). This experimental design has allowed us to estimate the timing of mtDNA mutations, drift, and selection with unprecedented precision. Our results are remarkably concordant between 2 complementary population-genetic approaches. We find evidence for a severe germline bottleneck (7–10 mtDNA segregating units) that occurs independently in different oocyte lineages from the same mother, while somatic bottlenecks are less severe. We demonstrate that divergence between mother and offspring increases with the mother’s age at childbirth, likely due to continued drift of heteroplasmy frequencies in oocytes under meiotic arrest. We show that this period is also accompanied by mutation accumulation leading to more de novo mutations in children born to older mothers. We show that heteroplasmic variants at intermediate frequencies can segregate for many generations in the human population, despite the strong germline bottleneck. We show that selection acts during germline development to keep the frequency of putatively deleterious variants from rising. Our findings have important applications for clinical genetics and genetic counseling.

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy–informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration.

BACKGROUND AND OBJECTIVES In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children METHODS Fatalities in children RESULTS Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children CONCLUSIONS Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.

The aim of this study was to test whether the Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention, delivered to parents of firstborn children, is associated with the BMI of first- and second-born siblings during infancy.Participants included 117 firstborn infants enrolled in a randomized controlled trial and their second-born siblings enrolled in an observation-only ancillary study. The RP curriculum for firstborn children included guidance on feeding, sleep, interactive play, and emotion regulation. The control curriculum focused on safety. Anthropometrics were measured in both siblings at ages 3, 16, 28, and 52 weeks. Growth curve models for BMI by child age were fit.Second-born children were delivered 2.5 (SD 0.9) years after firstborns. Firstborn and second-born children whose parents received the RP intervention with their first child had BMI that was 0.44 kg/m2 (95% CI: -0.82 to 0.06) and 0.36 kg/m2 (95% CI: -0.75 to 0.03) lower than controls, respectively. Linear and quadratic growth rates for BMI for firstborn and second-born cohorts were similar, but second-born children had a greater average BMI at 1 year of age (difference = -0.33 [95% CI: -0.52 to -0.15]).A RP educational intervention for obesity prevention delivered to parents of firstborns appears to spill over to second-born siblings.

Studies from diverse cultures report mixed results in the relationship between birth order and risk for obesity. Explanations may thus lie in the postnatal period when growth is shaped by the family environment, including parental feeding practices, which may be affected by siblings. Consistent with a family systems perspective, we describe two processes that may explain birth order effects on parental feeding practices and child outcomes: learned experience and resource dilution. Parents learn from experience when earlier-born children influence their parents’ knowledge, expectations, and behavior toward later-born siblings through their behaviors and characteristics—which can have both positive and negative implications. Resource dilution is a process whereby the birth of each child limits the time, attention and other resources parents have to devote to any one of their children. The goal of this review is to provide a theoretical basis for examining potential sibling influences on parental responsive feeding toward developing recommendations for future research and practice aimed at preventing obesity throughout family systems.

Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were added to pediatric liquid single-ingredient acetaminophen formulations. The hypothesis of this study is that implementation would be associated with reduced volume and severity of pediatric acetaminophen exposures reported to the U.S. National Poison Data System.This study describes accidental unsupervised ingestions of acetaminophen in children aged6 years. Exposures were grouped into pre-implementation (pre-period; January 4, 2010-July 17, 2011); transition (July 18, 2011-July 15, 2012); and post-implementation (post-period; July 16, 2012-December 25, 2016) periods. Cumulative and annual rates of change per million units (i.e., bottles) sold were calculated for the pre- and post-periods for acetaminophen and pediatric liquid ibuprofen (comparator without flow restrictors). Pre- to post-period rate ratios were used to compare products and to estimate the potential effect on other over-the-counter medications. Analysis was conducted in 2017 and 2018.The pre- and post-period cumulative acetaminophen exposure rate was 507.2 (95% CI=481.1, 534.6) and 325.6 (95% CI=305.8, 346.7) per 1 million units sold, respectively. Declines in the pre- versus post-period rate ratios were seen for exposures with any effect (0.642, 95% CI=0.591, 0.696) and with clinically significant outcomes (0.728, 95% CI=0.581, 0.913). In the post-period, acetaminophen exposures decreased faster than ibuprofen with a rate of change ratio of 0.936 (95% CI=0.912, 0.960) for all exposures and 0.939 (95% CI=0.909, 0.970) for exposures with any effect.The addition of flow restrictors to pediatric liquid acetaminophen was associated with a reduction in the number and severity of exposures. Application of flow restrictors to other liquid medications should be considered.

Objective This study was undertaken to assess the potential value of preoperative blood components as prognostic markers of outcome after lung cancer resection, and hence their potential to aid in the selection of patients for curative surgery. Methods This was a single-center study on 313 patients who underwent surgery for non-small-cell lung cancer from 2006 to 2008. Data were analyzed retrospectively from a prospectively maintained thoracic database. Preoperative blood results including plasma fibrinogen levels, serum C-reactive protein, hemoglobin concentration, and platelet count were included in the analysis. Results The mean age was 75 years, and 40% of the patients were females. The most common resection was lobectomy in 68% of patients, followed by pneumonectomy, wedge resection, and segmentectomy in 18%, 10%, and 1.6%, respectively. Patients with abnormal C-reactive protein, fibrinogen, and hemoglobin levels had a worse overall survival. Large tumor size and nodal metastasis on clinical staging was also associated with poor survival. However, on Cox regression analysis, plasma fibrinogen and nodal metastasis were the only independent predictors of survival after lung resection. Conclusions Among the different blood markers, elevated preoperative plasma fibrinogen was an independent marker of reduced survival in patients with resected non-small-cell lung cancer, and its value in selecting patients who may benefit from surgery needs further investigation.

Despite the known benefits of breastmilk, associations between breastfeeding and child overall health outcomes remain unclear. We aimed to understand associations between breastfeeding and health outcomes, including child weight, through age 3. Analysis included women (N = 3006) in the longitudinal, prospective First Baby Study from 2009 to 2014. For this analysis, breastfeeding initiation and duration were measured using self-reported data from the 1-, 6- and 12-month surveys; child illnesses were analyzed from the 6-, 12-, and 24-month interviews; height and weight at age 3 were used to determine overweight/obese (≥85th percentile) and obese (≥95th percentile). Adjusted logistic regressions were utilized to determine significance. Greater duration of breastfeeding was associated with fewer reported acute illnesses at 6 months (p 0.001) and fewer diarrheal illness/constipation episodes at 6, 12, and 24 months (p = 0.05) in adjusted analyses. Fewer breastfed children, compared to non-breastfed children, were overweight/obese (23.5% vs. 37.8%; p = 0.032) or obese (9.1% vs. 21.6%; p = 0.012) at age 3. Breastfeeding duration was negatively associated with overweight/obese (never breastfed: 37.8%, 0-6 months: 26.9%,6 months: 20.2%; p = 0.020) and obesity (never breastfed: 21.6%, 0-6 months: 11.0%,6 months: 7.3%; p = 0.012). Overall, our findings support the hypothesis that duration of breastfeeding is associated with fewer reported acute illnesses at 6 months of age and diarrheal illness and/or constipation episodes at 6, 12, and 24 months. Additionally, results from our study suggest a protective effect of breastfeeding from childhood overweight/obesity, as children who received breastmilk for 6 months or longer had lower odds of overweight/obesity at age 3 years.

BACKGROUND AND OBJECTIVES: The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the National Institutes of Health sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. In this investigation, we evaluate racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies. METHODS: Data were obtained for all participants enrolled in 33 federally funded studies of drugs and devices conducted from 2008 through June 2020. Observed racial and ethnic distributions were compared with expected distributions by sampling Census data at the same geographic frequency as in the studies. Racial and ethnic enrollment was examined by demography, geography, study type, study burden, and expected bias. Standard descriptive statistics, χ2, generalized linear models, and linear regression were applied. RESULTS: A total of 10 918 participants (51% male, 6.6 ± 8.2 years) were enrolled across 46 US states and 4 countries. Studies ranged from treatment outcome reviews to randomized, placebo-controlled trials. Minority enrollment was comparable to, or higher than, expected (+0.1% to +2.6%) for all groups except Asian Americans (−3.7%, P < .001). American Indian and Alaskan Native and multiracial enrollment significantly increased over the evaluation period (P < .01). There were no significant differences in racial distribution as a function of age or sex, although differences were observed on the basis of geography, study type, and study burden. CONCLUSIONS AND RELEVANCE: This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation’s expectation to ensure adequate representation of all children.

Background Maternal glucose intolerance during pregnancy has been associated with developmental delays and impairments in offspring including worse motor function and a greater likelihood of inattention and/or hyperactivity. The First Baby Study recruited an observational cohort 3006 women during their first pregnancy and followed maternal-child dyads for 3 years. We sought to evaluate associations between diabetes during pregnancy and subjective concern for developmental delay among offspring at ages …

Women with excessive gestational weight gain (GWG) are at risk for poor psychosocial well-being and postpartum weight retention (PPWR). Scant research has examined longitudinal interrelations of GWG, psychosocial factors, and PPWR. This study examined: (a) pre-pregnancy weight status (ie, normal, overweight, obesity) differences in PPWR and its psychosocial determinants (perceived social support, perceived stress, depression) in women with excessive GWG (ie, above 2009 Institute of Medicine guidelines); and (b) whether GWG mediated associations between psychosocial determinants and PPWR. Women (N = 1352) reported third trimester perceived social support, perceived stress, and depressive symptoms, GWG, and 6- and 12-month PPWR via telephone interviews. Multivariate ANOVA analyses showed women with normal weight had higher 6-month PPWR than women with obesity; univariate ANOVA showed no group differences in psychosocial factors. Hayes mediation analyses indicated that GWG mediated the association between perceived stress and PPWR in women with overweight but not women with normal weight or obesity; perceived stress predicted GWG, and in turn, PPWR. Prenatal perceived stress may be a modifiable target of GWG and PPWR. Future research is needed to examine the utility of tailoring perinatal weight regulation interventions to reduce perceived stress in pregnant women with overweight.

Obesity is a highly heritable condition that affects increasing numbers of adults and, concerningly, of children. However, only a small fraction of its heritability has been attributed to specific genetic variants. These variants are traditionally ascertained from genome-wide association studies (GWAS), which utilize samples with tens or hundreds of thousands of individuals for whom a single summary measurement (e.g., BMI) is collected. An alternative approach is to focus on a smaller, more deeply characterized sample in conjunction with advanced statistical models that leverage longitudinal phenotypes. Novel functional data analysis (FDA) techniques are used to capitalize on longitudinal growth information from a cohort of children between birth and three years of age. In an ultra-high dimensional setting, hundreds of thousands of single nucleotide polymorphisms (SNPs) are screened, and selected SNPs are used to construct two polygenic risk scores (PRS) for childhood obesity using a weighting approach that incorporates the dynamic and joint nature of SNP effects. These scores are significantly higher in children with (vs. without) rapid infant weight gain—a predictor of obesity later in life. Using two independent cohorts, it is shown that the genetic variants identified in very young children are also informative in older children and in adults, consistent with early childhood obesity being predictive of obesity later in life. In contrast, PRSs based on SNPs identified by adult obesity GWAS are not predictive of weight gain in the cohort of young children. This provides an example of a successful application of FDA to GWAS. This application is complemented with simulations establishing that a deeply characterized sample can be just as, if not more, effective than a comparable study with a cross-sectional response. Overall, it is demonstrated that a deep, statistically sophisticated characterization of a longitudinal phenotype can provide increased statistical power to studies with relatively small sample sizes; and shows how FDA approaches can be used as an alternative to the traditional GWAS.

Expert guidance encourages interventions promoting structure-based practices to establish predictable eating environments in order to foster children's self-regulatory skills. However, few studies have examined whether and how child characteristics may moderate effects of interventions on maternal feeding practices. This analysis aimed to examine the effect of the INSIGHT Responsive Parenting (RP) intervention delivered largely during infancy, on child appetitive traits at 2.5 years and maternal feeding practices at 3 years. Primiparous mother-newborn dyads were randomized to a RP intervention designed for obesity prevention or a safety control intervention. Mothers completed the Child Eating Behavior Questionnaire at 2.5 years and the Structure and Control in Parent Feeding Questionnaire at 3 years. T-tests assessed study group differences on child appetitive traits at 2.5 years and maternal feeding practices at age 3. ANCOVA models assessed the effect of study group on parent feeding practices and tested appetitive traits as a moderator. Two hundred thirty-two mother-child dyads completed the trial. Mothers were predominantly white, non-Hispanic, college educated, and married. RP group mothers used more consistent meal routines, and less pressure, food to soothe, and food as reward compared to controls. Child satiety responsiveness moderated the RP intervention effect on maternal use of limiting exposure to unhealthy foods such that the RP intervention was most effective for children at higher levels of satiety responsiveness. Food responsiveness moderated RP intervention effects on maternal use of pressure, such that at lower levels of food responsiveness, control group mothers used more pressure than RP mothers. The INSIGHT RP intervention demonstrated sustained effects on maternal feeding practices through age 3 years, with some intervention effects showing moderation by child appetitive traits.

An amendment to this paper has been published and can be accessed via the original article.