Household food insecurity is associated with obesogenic health behaviours among a low-income cohort of pregnant women in Boston, MA.

OBJECTIVE: To examine associations of household food insecurity with health and obesogenic behaviours among pregnant women enrolled in an obesity prevention programme in the greater Boston area. DESIGN: Cross-sectional evaluation. Data were collected from structured questionnaires that included a validated two-item screener to assess household food insecurity. We used separate multivariable linear and logistic regression models to quantify the association between household food insecurity and maternal health behaviours (daily consumption of fruits and vegetables, sugar-sweetened beverages and fast food, physical activity, screen time, and sleep), mental health outcomes (depression and stress), hyperglycaemia status and gestational weight gain. SETTING: Three community health centres that primarily serve low-income and racial/ethnic minority patients in Revere, Chelsea and Dorchester, Massachusetts. PARTICIPANTS: Totally, 858 pregnant women participating in the First 1,000 Days program, a quasi-experimental trial. RESULTS: Approximately 21 % of women reported household food insecurity. In adjusted analysis, household food insecurity was associated with low fruit and vegetable intake (ß = -0·31 daily servings; 95 % CI -0·52, -0·10), more screen time (ß = 0·32 daily hours; 95 % CI 0·04, 0·61), less sleep (ß = -0·32 daily hours; 95 % CI -0·63, -0·01), and greater odds of current (adjusted odds ratio (AOR) 4·42; 95 % CI 2·33, 8·35) or past depression (AOR 3·01; 95 % CI 2·08, 4·35), and high stress (AOR 2·91; 95 % CI 1·98, 4·28). CONCLUSIONS: In our sample of mostly low-income, racial/ethnic minority pregnant women, household food insecurity was associated with mental health and behaviours known to increase the likelihood of obesity.

Effects of the First 1000 Days Program, a systems-change intervention, on obesity risk factors during pregnancy.

BACKGROUND: First 1000 Days is a systems-oriented program starting in early pregnancy lasting through the first 24 months of infancy focused on preventing obesity and related risk factors among low income, mother-infant pairs. The program was developed in partnership with stakeholders to create an infrastructure for system-wide change. It includes screening for adverse health behaviors and socio-contextual factors, patient navigation and educational materials to support behavior change and social needs, and individualized health coaching for women at highest risk of obesity and has been shown to reduce excess gestational weight gain for women who were overweight at the start of their pregnancy. The purpose of this study was to examine changes from the first to third trimester for women participating in the First 1000 Days Program. METHODS: We collected information through self-administered questionnaires during the first and third trimester of gestation and from electronic health records relating to obesity risk factors. Measures collected included behavior (i.e., diet, physical activity and screen time) and psychosocial (i.e., anxiety) outcomes, as well as enrollment in Women, Infant, and Children (WIC) program. We examined the extent to which participation in the program was associated with changes in behaviors and psychosocial outcomes among women during pregnancy. RESULTS: Women completed surveys at their initial and third trimester prenatal visits (n = 264). Mean age (SD) was 30.2 (5.51) years and 75% had an annual household income of <$50,000. Mean pre-pregnancy body mass index (BMI) was 27.7 kg/m2 and 64% started pregnancy with a BMI ≥ 25 kg/m2. In multivariable adjusted models, we observed decreases in intake of sugary-drinks (- 0.95 servings/day; 95% CI: - 1.86, - 0.03) and in screen time (- 0.21 h/day; 95% CI: - 0.40, - 0.01), and an increase in physical activity (0.88 days/week; 95% CI: 0.52, 1.23) from the first to third trimester. We also observed a decrease in pregnancy-related anxiety score (- 1.06 units; 95% CI: - 1.32, - 0.79) and higher odds of enrollment in Women, Infant, and Children (WIC) program (OR: 2.58; 95% CI: 1.96, 3.41). CONCLUSIONS: Our findings suggest that a systems-oriented prenatal intervention may be associated with improvements in behaviors and psychosocial outcomes during pregnancy among low-income mothers. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT03191591 ; Retrospectively registered on June 19, 2017).

Twelve-Month Outcomes of the First 1000 Days Program on Infant Weight Status.

OBJECTIVES: To examine the effects of the First 1000 Days intervention on the prevalence of infant overweight and maternal postpartum weight retention and care. METHODS: Using a quasi-experimental design, we evaluated the effects of the First 1000 Days program among 995 term, low-income infants and their mothers receiving care in 2 intervention community health centers and 650 dyads in 2 comparison health centers. The program includes staff training, growth tracking, health and behavioral screening, patient navigation, text messaging, educational materials, and health coaching. Comparison centers implemented usual care. Infant outcomes were assessed at 6 and 12 months, including weight-for-length z score and overweight (weight for length ≥97.7th percentile). We also examined maternal weight retention and receipt of care 6 weeks' post partum. RESULTS: The mean birth weight was 3.34 kg (SD 0.45); 57% of infants were Hispanic; 66% were publicly insured. At 6 months, infants had lower weight-for-length z scores (ß: -.27; 95% confidence interval [CI]: -.39 to -.15) and lower odds of overweight (adjusted odds ratio [OR]: 0.46; 95% CI: 0.28 to 0.76) than infants in comparison sites; differences persisted at 12 months (z score ß: -.18; 95% CI: -.30 to -.07; adjusted OR for overweight: 0.60; 95% CI: 0.39 to 0.92). Mothers in the intervention sites had modestly lower, but nonsignificant, weight retention at 6 weeks' post partum (ß: -.51 kg; 95% CI: -1.15 to .13) and had higher odds (adjusted OR: 1.50; 95% CI: 1.16 to 1.94) of completing their postpartum visit compared with mothers in the comparison sites. CONCLUSIONS: An early-life systems-change intervention combined with coaching was associated with improved infant weight status and maternal postpartum care.

Expectant Fathers' Social Determinants of Health in Early Pregnancy.

This cross-sectional, descriptive study examined unmet social and economic needs and health information requests of low-income, expecting fathers who participated in the First 1000 Days program. The First 1000 Days is a systems-level intervention aiming to prevent obesity among low-income mothers and infants across 3 community health centers in Greater Boston, MA, USA. Fathers who attended their partner's first prenatal care visit were invited to complete a program survey during early pregnancy. Among 131 fathers surveyed, 45% were white, 21% were Hispanic/Latino, 55% were foreign-born, and 69% reported an annual income under $50 000. Fathers reported elevated levels of food insecurity (18%) and 33% were unaware of someone that could provide a $50 loan; however, over 85% of fathers knew someone that could provide non-financial social support. Fathers requested information about pregnancy, birth preparation, and fatherhood. Findings support addressing fathers' unmet needs during pregnancy and providing father-specific perinatal information.

Self-reported barriers to accessing infertility care: patient perspectives from urban gynecology clinics.

PURPOSE: (1) To test the hypothesis that under-represented minority women, including Hispanic/Latina and African American or Black women, will be more likely to report greater socioeconomic and cultural barriers to infertility care compared with white women. (2) To identify gaps in knowledge that can guide future educational interventions. METHODS: A cross-sectional survey was completed by 242 women, ages 18-44, at five gynecology clinics in the greater Boston, Massachusetts area from February 27, 2018, to February 25, 2019. RESULTS: Of the respondents, 61.4% identified as Hispanic/Latina, 24.5% as white, and 6.6% as Black or African American. Cost was the most commonly reported barrier to care (62.8%) regardless of race/ethnicity or insurance status. Only 8.9% of participants were aware of personal insurance coverage for infertility treatment. Compared with white patients, Hispanic/Latina patients were less likely to know if their own insurance covered infertility treatment: 14.3% vs 6.8%; aRR 0.36 (95% CI 0.17-0.74), after adjusting for a personal history of infertility. CONCLUSION: Cost was the most commonly reported barrier to care. Most women were unaware of their insurance coverage despite the state insurance mandate to cover infertility treatment in Massachusetts. Education and outreach will be instrumental in helping address disparities in access to care.

Psychosocial status and prenatal care of unintended pregnancies among low-income women.

BACKGROUND: Nearly half of all pregnancies in the United States are reported as unintended and rates are highest among women of low socioeconomic status. The purpose of this study was to examine the associations between unintended pregnancies and maternal mental health and timing of prenatal care among low-income women. METHODS: In this cross-sectional study, 870 women, whom were participating in the First 1000 Days program in three community health centers in the Boston area, were enrolled at their first prenatal visit from August 2016 - September 2017. We assessed pregnancy intention by self-report using the Pregnancy Risk Assessment Monitoring System. We used self-reported survey information and electronic health record data to assess the following outcomes: current stress, current depression, and timing of initial prenatal visit. We used multivariable logistic regression models to examine associations and adjusted for sociodemographic factors. RESULTS: Women were a mean (SD) age of 29.3 (6.1), and 39.2% reported that their pregnancy was unintended. 50.6% of women were Hispanic, 28.4% were White, 10.1% were Black, and 10.9% were other races. 78.9% of women reported an annual household income <$50,000. Overall, 26.7% of women reported current stress, 8.2% reported current depression, and 18.3% of women initiated prenatal care after their first trimester. In multivariable analyses, women with unintended pregnancies had higher odds of experiencing current stress (OR: 1.72; 95% CI: 1.22, 2.41), current depression (OR: 1.83; 95% CI: 1.04, 3.20), and initiation of prenatal care post-first trimester (OR: 1.84; 95% CI: 1.23, 2.74). CONCLUSIONS: Unintended pregnancies were associated with current stress and depression, and delayed prenatal care in this sample of low-income women suggesting the importance of identifying high-risk women and tailoring interventions to support women's needs. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03191591; Retrospectively registered on June 19, 2017).

Association of the First 1,000 Days Systems-Change Intervention on Maternal Gestational Weight Gain.

OBJECTIVE: To examine the associations of a clinical and public health systems-change intervention on the prevalence of excess gestational weight gain among high-risk, low-income women. METHODS: In a quasi-experimental trial, we compared the prevalence of excess gestational weight gain among women before (n=643) and after (n=928) implementation of the First 1,000 Days program in two community health centers in Massachusetts. First 1,000 Days is a systematic program starting in early pregnancy and lasting through the first 24 months of childhood to prevent obesity among mother-child pairs. The program includes enhanced gestational weight gain tracking and counseling, screening for adverse health behaviors and sociocontextual factors, patient navigation and educational materials to support behavior change and social needs, and individualized health coaching for women at high risk for excess gestational weight gain based on their prepregnancy body mass index (BMI) or excess first-trimester weight gain. The primary outcome was gestational weight gain greater than the 2009 Institute of Medicine (now known as the National Academy of Medicine) guidelines according to prepregnancy BMI. RESULTS: Among 1,571 women in the analytic sample, mean (SD) age was 30.0 (5.9) years and prepregnancy BMI was 28.1 (6.1); 65.8% of women started pregnancy with BMIs of 25 or higher, and 53.2% were Hispanic. We observed a lower prevalence (55.8-46.4%; unadjusted odds ratio [OR] 0.69, 95% CI 0.49-0.97), similar to results in a multivariable analysis (adjusted OR 0.69, 95% CI 0.49-0.99), of excess gestational weight gain among women with prepregnancy BMIs between 25 and 29.9. Among women who were overweight at the start of pregnancy, the lowest odds of excess gestational weight gain were observed among those with the most interaction with the program's components. Program enrollment was not associated with reduced excess gestational weight gain among women with prepregnancy BMIs of 30 or higher. CONCLUSIONS: Implementation of a systems-change intervention was associated with modest reduction in excess gestational weight gain among women who were overweight but not obese at the start of pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03191591.

Development of an Immunohistochemical Assay to Detect the Ataxia-Telangiectasia Mutated (ATM) Protein in Gastric Carcinoma.

Ataxia-telangiectasia mutated (ATM), a key activator of DNA damage response mechanisms, represents a potential biomarker for targeted gastric carcinoma therapies. A phase II study (Study 39; NCT01063517) designed to investigate the combination olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer did not meet its primary endpoint of progression-free survival; however, an improvement in the secondary endpoint of overall survival was recorded with a greater overall survival benefit noted in patients with ATM-negative tumors. An ATM immunohistochemical (IHC) diagnostic assay was developed to identify patients who may respond favorably to targeted therapies and deployed in the confirmatory phase III GOLD trial (NCT01924533). The VENTANA ATM (Y170) assay was developed for investigational use in formalin-fixed, paraffin-embedded gastric carcinoma samples using an anti-ATM rabbit monoclonal antibody (clone Y170) and was optimized with OptiView DAB IHC Detection Kit on a BenchMark ULTRA instrument. The assay was deployed in studies assessing sensitivity, specificity, robustness, precision, and determining optimal ATM staining cutoff to define ATM-deficiency (ATM-low). The ATM (Y170) assay met all predefined product development acceptance criteria. Multiple parameters were characterized, including repeatability, reproducibility, analytical sensitivity, specificity, robustness, and product stability. The scoring algorithm was defined; gastric carcinoma samples were considered ATM-negative or ATM-positive when <25% or ≥25%, respectively, of tumor cell nuclei expressed ATM at any IHC stain intensity and nuclei of immune and/or endothelial cells expressed ATM at a moderate stain intensity (internal positive control). Results highlight reproducibility of the assay, supporting suitability for investigational use for evaluation of gastric carcinoma samples using tumor cell staining cutoff of <25% to define ATM-deficiency. Using this ATM assay, phase III GOLD trial (NCT01924533) clinical trial did not meet its primary endpoint, only suggesting, but not demonstrating, that assessment of ATM levels by IHC could possibly be useful in assessing the degree of benefit that may be achieved by adding olaparib to paxitaxel when treating gastric carcinoma. The utility of ATM (Y170) assay as a companion diagnostic requires further clinical validation.

Identification of substance use disorders among pregnant women: A comparison of screeners.

BACKGROUND: The purpose of this study is to evaluate five self-report, non-proprietary questionnaires in the identification of substance use disorders [including alcohol, cannabis, opioids, and stimulants] among pregnant women. PROCEDURES: A total of 1220 pregnant women completed the NIDA Quick Screen, CRAFFT, Substance Use Risk Profile-Pregnancy (SURP-P), Wayne Indirect Drug Use Questionnaire (WIDUS), and the 5 Ps, as well as the MINI diagnostic interview for substance use disorders, which served as the reference standard. Measures of merit calculated for each screener included sensitivity, specificity, accuracy, and area under the receiver operating curve (AUROC). MAIN FINDINGS: The participants were socioeconomically diverse, with a mean age of 29 years. Over 15% met diagnostic criteria for a substance use disorder. AUROCS for identifying any substance use disorder (including alcohol) ranged from a high of 0.75 for the CRAFFT (95% CI = 0.72-79) and 0.74 for the SURP-P (95% CI = 0.71-.78) to a low of 0.62 for the NIDA Quick Screen (95% CI = 0.59-.65). Overall accuracy of most tested measures was higher for identification of alcohol use disorders than for other substance use disorders (e.g., AUROCs for the CRAFFT and SURP-P for identifying alcohol use disorders were 0.78 and 0.77, respectively). PRINCIPAL CONCLUSIONS: The CRAFFT and SURP-P showed modest ability to identify substance use disorders among pregnant women. Future research is needed to develop an ideal questionnaire set in the complicated societal context which includes increasing rates of use and potential sanction.

Accuracy of five self-report screening instruments for substance use in pregnancy.

BACKGROUND AND AIMS: The accuracy of current screening instruments for identification of substance use in pregnancy is unclear, particularly given methodological shortcomings in existing research. This diagnostic accuracy study compared five existing instruments for ability to identify illicit drug, opioid and alcohol use, under privacy expectations consistent with applied practice and using a gold standard incorporating toxicological analysis. DESIGN: Prospective cross-sectional screening accuracy study. SETTING: Three sites encompassing four prenatal care clinics in the United States. PARTICIPANTS: Convenience sample of 1220 racially, ethnically and socio-economically diverse pregnant women aged 18 years and over. MEASUREMENTS: In Phase I, participants completed the five screening instruments in counterbalanced order. Instruments included the Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT (acronym for five-item screener with items related to car, relax, alone, forget, friends and trouble), 5Ps (parents, peers, partner, pregnancy, past), Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (NIDA) Quick Screen. In Phase II, participants provided a urine sample and completed a calendar recall-based interview regarding substance use. These screeners were tested, using receiver operating characteristic (ROC) analysis and accuracy statistics, against a reference standard consisting of substance use in three classes (illicit drugs, opioids and alcohol), considered positive if use was evident via 30-day calendar recall or urine analysis. FINDINGS: Three hundred and fifteen of 1220 participants (26.3%) met reference standard criteria for positivity. The single-item screening questions from the NIDA Quick Screen showed high specificity (0.99) for all substances, but very poor sensitivity (0.10-0.27). The 5Ps showed high sensitivity (0.80-0.88) but low specificity (0.35-0.37). The CRAFFT, SURP-P and 5Ps had the highest area under the curve (AUC) for alcohol (0.67, 0.66 and 0.62, respectively), and the WIDUS had the highest AUC for illicit drugs and opioids (0.70 and 0.69, respectively). Performance of all instruments varied significantly with race, site and economic status. CONCLUSIONS: Of five screening instruments for substance use in pregnancy tested (Substance Use Risk Profile-Pregnancy (SURP-P), CRAFFT, 5Ps, Wayne Indirect Drug Use Screener (WIDUS) and the National Institute on Drug Abuse (Quick Screen), none showed both high sensitivity and high specificity, and area under the curve was low for nearly all measures.

Strengthening integration of clinical and public health systems to prevent maternal-child obesity in the First 1,000Days: A Collective Impact approach.

INTRODUCTION: Obesity interventions may be most effective if they begin in the earliest stages of life, support changes across family, clinical, and public health systems, and address socio-contextual factors. METHODS: The First 1000Days is a systematic program starting in early pregnancy lasting through the first 24months of infancy to prevent obesity among low-income mother-infant pairs in three community health centers in Massachusetts. The program uses a Collective Impact approach to create the infrastructure for sustained, system-wide changes for obesity prevention across early life clinical and public health services, including Obstetrics, Pediatrics, Adult Medicine, Behavioral Health, Nutrition, Community Health, the Women, Infants and Children (WIC) program, and the Maternal, Infant and Childhood Home Visiting program. Program components include 1) staff and provider training; 2) enhanced gestational weight gain and infant overweight tracking; 3) universal screening of adverse health behaviors and socio-contextual factors; 4) universal patient navigation to support individual behavior change and social needs, while strengthening integration of clinical and public health services; 5) individualized health coaching for mother-infant pairs at high risk of obesity; and 6) educational materials to support behavior change. RESULTS: A quasi-experimental evaluation design will examine changes, between 2015 and 2019, in gestational weight gain and prevalence of infant overweight from 0 to 24months of age. CONCLUSIONS: The First 1000Days program will examine the effectiveness of an early life obesity prevention program for mother-infant pairs. If successful, the program could provide a model for chronic disease prevention and health promotion among vulnerable families starting in early life.

Intensive Prenatal Nutrition Counseling in a Community Health Setting: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of a culturally appropriate nutritional intervention delivered to overweight and obese patients in a community health setting on gestational weight gain and postpartum weight retention. MATERIALS AND METHODS: We conducted a randomized controlled trial of an intensive nutrition counseling intervention for overweight and obese women by a registered dietitian throughout pregnancy and 6 months postpartum. The primary outcome was likelihood of gestational weight gain within Institute of Medicine (IOM, now known as the Health and Medicine Division of the National Academies of Sciences, Engineering, and Medicine) guidelines. Secondary outcomes included birth weight and maternal and neonatal complications. RESULTS: Three hundred patients were randomized. In intent-to-treat analyses, assignment to the intervention group did not have a significant effect on maintenance of gestational weight gain within IOM guidelines (34.2% compared with 27.5%, odds ratio [OR] 1.4, 95% CI 0.8-2.4). Among obese women, assignment to the intervention group was associated with fewer large-for-gestational-age (LGA) neonates (7% compared with 17%; OR 0.3, 95% CI 0.1-0.99). Neither primary nor secondary outcomes were significantly different among overweight women in the intervention group in intent-to-treat analyses. In as-treated analyses, women in the intervention group had lower neonatal birth weights (3,343 g compared with 3,500 g; difference -157.4 g, 95% CI -298.4 to -16.5) and lower likelihood of LGA (6% compared with 14%; OR 0.4, 95% CI 0.2-0.96). Among overweight women, participation in the intervention was associated with lower gestational weight gain (26.1 pounds compared with 31.4 pounds; difference -5.3 pounds, 95% CI -10.0 to -0.6), lower neonatal birth weights (3,237 g compared with 3,467 g; difference -230, 95% CI -452.8 to -7.8), and lower percent of initial body mass index at 6 months postpartum (101% compared with 106%; difference -4.9, 95% CI -8.8 to -0.9). CONCLUSION: Our intervention did not result in a significant improvement in our primary outcome, the proportion of obese and overweight women who had gestational weight gain within IOM guidelines. However, intensive prenatal nutrition counseling offered in an urban community health setting may decrease LGA births among a group of overweight and obese women from culturally diverse backgrounds at risk for adverse maternal and neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01056406.

Women's Use of Health Care in the First 2 Years Postpartum: Occurrence and Correlates.

Objectives We sought to determine rates and correlates of accessing health care in the 2 years following delivery among women at an urban academic medical center. Methods We used electronic medical records, discharge, and billing data to determine the occurrence of primary care, other non-primary outpatient care, emergency department visits, and inpatient admissions among women delivering at a single medical center who had a known primary care affiliation to that medical center over a 5 year period. We explored sociodemographic, clinical, and health care-related factors as correlates of care, using bivariate and multivariable modeling. Results Of 6216 women studied, most (91 %) had had at least one health care visit in the window between 2 months and 2 years postpartum (the "late postpartum period"). The majority (81 %) had had a primary care visit. Factors associated with use of health care in this period included a chronic medical condition diagnosed prior to pregnancy (adjusted odds ratio (AOR) 1.42, 95 % CI [1.19, 1.71]), prenatal care received in an urban community health center (AOR 1.35 [1.06, 1.73]), having received obstetric (AOR 1.90 [1.51, 2.37]), primary (AOR 2.30 [1.68, 3.23]), or other non-primary outpatient care (AOR 2.35 [1.72, 3.39]) in the first 2 months postpartum, and living closer to the hospital [AOR for residence >17.8 miles from the medical center (AOR 0.74 [0.61, 0.90])]. Having had an obstetrical complication did not increase the likelihood of receipt of care during this window. Conclusions for Practice Among women already enrolled in a primary care practice at our medical center, health care utilization in the late postpartum period is high, but not universal. Understanding the characteristics of women who return for health care during this window, and where they are seen, can improve transitions of care across the life course and can provide opportunities for important and consistent interconception and well-woman messaging.

Interventions for Childhood Obesity in the First 1,000 Days A Systematic Review.

CONTEXT: The "first 1,000 days"-conception through age 24 months-are critical for the development and prevention of childhood obesity. This study systematically reviews existing and ongoing interventions during this period, identifies gaps in current research, and discusses conceptual frameworks and opportunities for future interventions. EVIDENCE ACQUISITION: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched to identify completed and ongoing interventions implemented during pregnancy through age 24 months that aimed to prevent overweight/obesity between ages 6 months and 18 years. English-language, controlled interventions published between January 1, 1980 and December 12, 2014, were analyzed between December 13, 2014 and March 15, 2015. EVIDENCE SYNTHESIS: Of 34 completed studies from 26 unique identified interventions, nine were effective. Effective interventions focused on individual- or family-level behavior changes through home visits, individual counseling or group sessions in clinical settings, a combination of home and group visits in a community setting, and using hydrolyzed protein formula. Protein-enriched formula increased childhood obesity risk. Forty-seven ongoing interventions were identified. Across completed and ongoing interventions, the majority target individual- or family-level changes, many are conducted in clinical settings, and few target early-life systems and policies that may impact childhood obesity. CONCLUSIONS: Obesity interventions may have the greatest preventive effect if begun early in life. Yet, few effective interventions in the first 1,000 days exist, and many target individual-level behaviors of parents and infants. Interventions that operate at systems levels and are grounded in salient conceptual frameworks hold promise for improving future models of early-life obesity prevention.

Risk Factors for Childhood Obesity in the First 1,000 Days: A Systematic Review.

CONTEXT: Mounting evidence suggests that the origins of childhood obesity and related disparities can be found as early as the "first 1,000 days"-the period from conception to age 2 years. The main goal of this study is to systematically review existing evidence for modifiable childhood obesity risk factors present from conception to age 2 years. EVIDENCE ACQUISITION: PubMed, Embase, and Web of Science were searched for studies published between January 1, 1980, and December 12, 2014, of childhood obesity risk factors present during the first 1,000 days. Prospective, original human subject, English-language research with exposure occurrence during the first 1,000 days and with the outcome of childhood overweight or obesity (BMI ≥85th percentile for age and sex) collected between age 6 months and 18 years were analyzed between December 13, 2014, and March 15, 2015. EVIDENCE SYNTHESIS: Of 5,952 identified citations, 282 studies met inclusion criteria. Several risk factors during the first 1,000 days were consistently associated with later childhood obesity. These included higher maternal pre-pregnancy BMI, prenatal tobacco exposure, maternal excess gestational weight gain, high infant birth weight, and accelerated infant weight gain. Fewer studies also supported gestational diabetes, child care attendance, low strength of maternal-infant relationship, low SES, curtailed infant sleep, inappropriate bottle use, introduction of solid food intake before age 4 months, and infant antibiotic exposure as risk factors for childhood obesity. CONCLUSIONS: Modifiable risk factors in the first 1,000 days can inform future research and policy priorities and intervention efforts to prevent childhood obesity.

The validation of a novel method combining both HER2 immunohistochemistry and HER2 dual-colour silver in situ hybridization on one slide for gastric carcinoma testing.

BACKGROUND: HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide. METHODS: Immunohistochemistry (IHC) and HER2 dual-colour silver in situ hybridization (SISH) as single methods (IHC/SISH) and gene-protein platform combining both methods on one slide (gene/protein) were performed in randomly collected 100 cases of gastric adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining. RESULTS: 96 of 100 samples were assessable. In the gene/protein staining, pathologists were able to assess gene amplification and consequent protein expression at the single cell level. In comparison trials, gene amplification was observed in 14.6% by both, conventional SISH and gene/protein platform (agreement 100%; Kappa-coefficient κ = 1.0). Protein expression scores by IHC were 70.8% (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There were complete concordances in IHC assessment of cases with score 0 (100.0%; κ = 1). High concordances are shown in score 1+ (98.96%; κ = 0.947) and 3+ (96.88%; κ = 0.825) cases and good concordances in 2+ cases (95.83%; κ = 0.728). CONCLUSIONS: This novel combined platform has the advantage of being able to evaluate both gene and the protein status in the same cancer cell and may be of particular interest for research and patient's care. ARTICLE CATEGORY: Disease Biomarker.

Simultaneous analysis of HER2 gene and protein on a single slide facilitates HER2 testing of breast and gastric carcinomas.

This study sought to evaluate a new combined gene and protein detection platform in the context of HER2 evaluation in breast and gastric carcinomas. HER2 immunohistochemistry (IHC) and dual color in situ hybridization (Dual ISH) were combined on a single slide. Results were compared with conventional HER2 IHC and fluorescence ISH. Results from the gene and protein assay were reliable and highly reproducible for both breast and gastric carcinomas. Concordance was found between conventional HER2 IHC and ISH testing and the gene and protein assay in the same laboratory (>95% for Dual ISH; lower for IHC because of different antibody clones), between IHC and Dual ISH performed on the same slide (>92%), and in the gene and protein assays between laboratories (>96%). This cost- and time-effective method provides fast and definitive results (IHC confirmed by means of Dual ISH) to aid in rapid treatment decisions. It can also be applied to other gene and protein combinations.

Inhibition of the c-fms proto-oncogene autocrine loop and tumor phenotype in glucocorticoid stimulated human breast carcinoma cells.

The c-fms proto-oncogene encoded CSF-1 receptor and its ligand represent a feedback loop, which in a paracrine manner, is well known to promote spread of breast cancers. The role of the autocrine feedback loop in promotion of breast tumor behavior, in particular in vitro, is less well understood. The physiologic stimulation of c-fms expression by glucocorticoids (GCs) in vitro and in vivo magnifies the tumor promoting effect seen in these cells from activated c-fms signaling by CSF-1. Targeted molecular therapy against c-fms could therefore abrogate both complementary feedback loops. Using breast cancer cells endogenously co-expressing receptor and ligand, we used complementary approaches to inhibit c-fms expression and function within this autocrine pathway in the context of GC stimulation. Silencing RNA (shRNA), antisense oligonucleotide therapy (AON), and inhibition of c-fms signaling, were all used to quantitate inhibition of GC-stimulated adhesion, motility, and invasion of human breast cancer cells in vitro. shRNA to c-fms downregulated GC-stimulated c-fms mRNA by fourfold over controls, correlating with over twofold reduction in cellular invasiveness. AON therapy was also able to inhibit GC stimulation of c-fms mRNA, and resulted in threefold less invasiveness and 1.5 to 2-fold reductions in adhesion and motility. Finally, the small-molecule c-fms inhibitor Ki20227 was able to decrease in a dose-response manner, breast cancer cell invasion by up to fourfold. Inhibition of this receptor/ligand pair may have clinical utility in inhibition of the autocrine as well as the known paracrine interactions in breast cancer, thus further supporting use of targeted therapies in this disease.

Posttranscriptional suppression of proto-oncogene c-fms expression by vigilin in breast cancer.

cis-acting elements found in 3'-untranslated regions (UTRs) are regulatory signals determining mRNA stability and translational efficiency. By binding a novel non-AU-rich 69-nucleotide (nt) c-fms 3' UTR sequence, we previously identified HuR as a promoter of c-fms proto-oncogene mRNA. We now identify the 69-nt c-fms mRNA 3' UTR sequence as a cellular vigilin target through which vigilin inhibits the expression of c-fms mRNA and protein. Altering association of either vigilin or HuR with c-fms mRNA in vivo reciprocally affected mRNA association with the other protein. Mechanistic studies show that vigilin decreased c-fms mRNA stability. Furthermore, vigilin inhibited c-fms translation. Vigilin suppresses while HuR encourages cellular motility and invasion of breast cancer cells. In summary, we identified a competition for binding the 69-nt sequence, through which vigilin and HuR exert opposing effects on c-fms expression, suggesting a role for vigilin in suppression of breast cancer progression.