Diet and Physical Activity by Prediabetes Status Among U.S. Adolescents: National Health and Nutrition Examination Survey, 2007-2018.

Background: Prediabetes among adolescents is on the rise, yet it is unclear if modifiable risk factors vary by prediabetes status. Methods: This study examined associations between diet (primary objective) and physical activity (secondary objective) by prediabetes status among U.S. adolescents (12-19 years) who participated in the National Health and Nutrition Examination Survey from 2007-2018. Differences in Healthy Eating Index (HEI)-2015-2020 scores (total and 13 component scores), nutrients of public health concern, and physical activity were examined by prediabetes status (no prediabetes vs. prediabetes). Results: Adolescents (n = 2,487) with prediabetes had significantly lower whole grains component scores and intakes of vitamin D, phosphorus, and potassium (all p < .05), than adolescents without prediabetes. Physical activity levels were not optimal for either group, there were no differences by prediabetes status (n = 2,188). Conclusion: Diabetes prevention interventions for adolescents are needed and should promote a healthy diet target and encourage physical activity.

Substitution Modeling Shows Simple Dietary Changes Increase Mediterranean-Style Diet Pattern Scores for US Adults.

Background: A Mediterranean-style diet pattern (MSDP) is a recommended diet pattern in the 2020-2025 Dietary Guidelines for Americans. Few studies report widespread adherence to the diet, which suggests Americans may benefit from strategies to help them improve alignment to an MSDP. Objectives: The purpose of this study was to assess the impact of isocaloric food substitutions on adherence to an MSDP in US adults. Methods: Using data from NHANES (2007-2018), alignment to an MSDP was determined by calculation of a Mediterranean diet scoring index appropriate for non-Mediterranean populations (0-100 points for the total score, with higher scores indicating greater adherence). The sample was divided into 2 groups, a high-adherence group (HA) and a non-high-adherence group (nHA), to differentiate food groups to be used for isocaloric food substitution modeling. Substitution modeling via multiple regression analyses determined food selections that have the greatest impact on MSDP scores. Honey was added to the substitutions in recipe form and evaluated for its impact on MSDP scores. Results: The study consisted of 19,978 adults, ages 25-65, with complete dietary data. The nHA had a lower mean total MSDP score (7.07 ± 0.04 points) compared to the HA (16.45 ± 0.09 points). Increasing olive oil from nonuse to partial use had the greatest impact (>+2 points) for both groups. Other isocaloric substitutions also improved adherence, albeit to a lesser degree, including substituting 1 oz of whole grains for 1 oz of refined grains, 4 oz of fish for 4 oz of red meat, and 4.9 cups of kale for 0.7 cups of starchy or root vegetables. Improved MSDP scores were sustained when honey was added to the substitutions. Conclusions: Simple dietary substitutions can help a diet more closely align with an MSDP. Adding honey to the simple substitutions may increase palatability without sacrificing nutritional benefits.

Perspective: Utilizing High Amylose Wheat Flour to Increase Dietary Fiber Intake of Children and Adolescents: A Health by Stealth Approach.

Children and adolescents have consistently failed to meet recommended levels of dietary fiber consumption, thus making fiber a nutrient of concern. The importance of adequate dietary fiber intake to attain a healthy diet necessitates the identification of fiber-rich and readily consumed food sources by youth. Grain-based foods derived from whole grains represent a strategic initiative to increase dietary fiber consumption and is consistent with the American diet pattern. Increased intake of foods made from whole grains have been positively associated with improved health outcomes but are also less preferred among youth compared to refined grain products, which make up the majority of their carbohydrate intake. Advances in the commercialization and availability of high amylose wheat flour, a source of resistant starch fiber, provides an opportunity to remedy the suggested acceptability issues of whole grain products indicative of sensory factors, without compromising the amount of fiber ingested. Resistant starch fiber consumption has been associated with health benefits including improved blood sugar management, improved markers of digestive and gut health, increased satiety, and a reduced inflammatory response among adults. The limited studies that indicate fiber's direct benefit among youth are largely observational, thereby necessitating the need for more controlled trials for these age groups. Replacing traditional refined wheat flour with refined high amylose wheat flour has the unique ability to increase dietary fiber consumption without compromising desired sensory and finished product characteristics and thus can help increase dietary fiber consumption in children and adolescents who struggle to meet adequate intakes of fiber.

Frequency of Meals Prepared Away from Home and Nutrient Intakes among US Adolescents (NHANES 2011-2018).

Frequency of consuming foods prepared away from home has been associated with lower diet quality among adults and adolescents in several earlier studies. Nutrient and food group intake and Healthy Eating Index (HEI)-2015 scores were compared among a U.S. nationally representative sample of adolescents (12-19 years, n = 3975) by frequency of consuming food prepared away from home ≤2 times/week (n = 2311) versus >2 times/week (n = 1664) using National Health and Nutrition Examination Survey (NHANES) data from 2011-2018. Regression analyses were used to compare intakes among adolescents by frequency of eating meals prepared away from home adjusting for covariates. Older (16-19 years) vs. younger (12-15 years) adolescents and those from homes with higher vs. lower family income to poverty ratios had greater frequency of eating meals prepared away from home. Intakes of nutrients of concern for adolescents including choline, vitamin D, potassium, magnesium, fiber, phosphorus, folate, iron, and total HEI-2015 scores and component scores for total vegetables, and greens and beans were lower among adolescents who consumed meals prepared away from home more vs. less often. However, no differences were noted among food group intakes considered good sources of nutrients of concern such as total fruit, total vegetables, whole grains, and total dairy, except for beans and peas by frequency of eating foods prepared away from home. Greater frequency of eating foods prepared away from home was associated with lower diet quality among adolescents in a nationally representative sample of U.S. adolescents.

Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.

BACKGROUND: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited. METHODS: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race. RESULTS: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36). CONCLUSIONS: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

Diet Quality and Eating Practices among Hispanic/Latino Men and Women: NHANES 2011-2016.

Dietary quality of Hispanic/Latino adults residing in homes with children may differ by gender, that in turn, may impact youth through role modeling and food availability. Using a nationally representative sample (n = 1039) from the National Health and Nutrition Examination Survey (2011-2016), adjusted regression analyses were used to examine food-related practices, food group intake, and dietary quality among Hispanic/Latino men and women in homes with children (6-17 years). Compared to women, men had lower total 2015 Healthy Eating Index (HEI) scores and component HEI scores for healthy food groups. Men also ate more meals that were not home prepared/week and purchased more foods from non-grocery stores than women. Negative food-related practices and working more hours/week may explain in part the lower dietary quality observed among Hispanic/Latino men than women. Interventions may be improved by targeting gender-specific food-related behaviors that could positively impact dietary quality of youth residing with them.

Evening Meal Types and Family Meal Characteristics: Associations with Demographic Characteristics and Food Intake among Adolescents.

Evening meal types and family meal characteristics among adolescents may vary by demographic characteristics and weight status and can negatively impact dietary intake. We used cross-sectional Family, Life, Activity, Sun, Health, and Eating Study data from parent and adolescent dyads (12-17 years) to examine associations of adolescent evening meal types and family meal characteristics with adolescent and family demographic characteristics, weight status, and dietary intake. Multiple logistic regression models were used to evaluate associations of evening meal types and family meal characteristics with daily intake frequency of foods of interest, adolescent demographic characteristics, SES indicators, and weight status. All evening meal types that were not cooked from scratch showed associations with higher daily intake frequencies of less healthy food groups (fast food, convenience foods, sugar-sweetened beverages). Fast food eaten at home and heat-and-serve/box evening meals were associated with lower daily intake frequency of fruits and vegetables. Weight status, race/ethnicity, and age accounted for differences in associations with agreement regarding family meal characteristics. Agreement with often watching TV while eating, often eating alone and the importance of eating together were associated with daily intake frequency of some food groups. Evening meal types focused on convenience and negative family meal characteristics may adversely influence dietary intake among adolescents.

Latino adolescent-father discrepancies in reporting activity parenting practices and associations with adolescents' physical activity and screen time.

BACKGROUND: Latino fathers may play important roles in adolescents' physical activity and screen time. However, informant discrepancies regarding paternal activity parenting practices may challenge studies supporting evidence-based applications. This study examined Latino adolescent-father discrepancies in reporting paternal activity parenting practices, types of discrepancies by participant characteristics, and associations between discrepancy types and adolescents' physical activity and screen time. METHODS: The sample for this cross-sectional study included Latino early adolescents and their fathers (n = 138 dyads) from baseline data collected for a family-centered, healthy lifestyle intervention in a metropolitan area. In parallel measures, Latino adolescents and fathers reported paternal activity parenting practices related to expectation or allowance, behavioral modeling, and providing opportunities for physical activity or screen time. Level of agreement and discrepancies were examined using the percentage of agreement, weighted kappa statistics, Pearson correlation coefficients, and paired-sample t-tests. Undesirable discrepancy types included adolescents reporting lower scores for paternal physical activity parenting practices or higher scores for paternal screen time parenting practices than fathers. Participants' sociodemographic characteristics and weight status were compared by discrepancy type using between-group t-tests or Chi-square tests. Associations between discrepancy type and adolescents' physical activity and screen time were examined using multivariate regression analyses. RESULTS: The study sample was low-income with a high prevalence of overweight and obesity. Adolescent and paternal reports of activity parenting practices had poor agreement (percentages of agreement: 22.2-34.3%, weighted kappa statistics: < 0.2, and correlation coefficients: 0.06-0.25). An undesirable discrepancy type for certain parenting practices was more likely to be observed among fathers without full-time employment, girls, older adolescents, and adolescents and fathers within overweight or obese BMI categories. Discrepancies in paternal expectation regarding physical activity and allowance of screen time had adverse associations with adolescents' physical activity (ß = - 0.18, p = 0.008) and screen time (ß = 0.51, p <  0.001). CONCLUSION AND IMPLICATIONS: Discrepancies in reporting activity parenting practices were evident between Latino adolescents and their fathers, especially among certain sociodemographic and weight status groups. Adolescents' perceptions on paternal parenting practices tended to be better indicators of their activity levels than fathers' reports.

Diet and Physical Activity Behaviors Among Adolescent Transgender Students: School Survey Results.

PURPOSE: Diet and physical activity behaviors are determinants of health for adolescents; however, few studies have assessed these behaviors among transgender youth. This study examined dietary behaviors, physical activity, weight-based bullying, and weight status among four groups based on transgender and gender nonconforming (TGNC) status and birth-assigned sex. METHODS: Data were from a large cross-sectional, population-based, statewide survey of high school students (n = 80,794, Minnesota Student Survey, 2016). Comparisons were made for dietary and physical activity behaviors among TGNC and cisgender youth and among TGNC birth-assigned males and females and cisgender males and females. RESULTS: About 2.7% of the total survey respondents identified as TGNC. TGNC students were more likely to be ethnically diverse, not living with a biological parent, participating in free or reduced-price school meals, and skipping meals compared with cisgender students. TGNC youth reported less frequent intake of fruit and milk and more frequent intake of fast food and soft drinks than cisgender students. TGNC students were also more likely to be overweight or obese, bullied for weight or size, and less likely to be physically active compared with cisgender youth. TGNC birth-assigned males reported more frequent intake of fast food and soft drinks and less physical activity compared with TGNC birth-assigned females and cisgender boys and girls. CONCLUSIONS: TGNC students reported more negative health behaviors than cisgender students. Programs to address disparities in diet and physical activity behaviors may need to be tailored by gender identity and gender identity subgroups.

Frequency of Trying to Lose Weight and Its Association with Children's Weight Perception and Dietary Intake (NHANES 2011-2012).

Weight loss practices and frequency among children and adolescents can impact overall diet quality. We used cross-sectional U.S. National Health and Nutrition Examination Survey data (NHANES) 2011-2012 from 1303 children and adolescents (8-15 years) to examine associations between frequency of trying to lose weight (never vs. sometimes/a lot) and sociodemographic characteristics, self-perception of weight, and dietary intake. A greater frequency of trying to lose weight was reported by participants with overweight/obesity, those from households with lower annual income and those who perceived they were overweight or obese compared to their counterparts. A high proportion of participants with overweight and obesity considered themselves to be "about the right weight" (76.7 and 42.8%, respectively). Intake data based on one 24-h dietary recall were examined using multivariable regression models adjusted for child and parent/family characteristics. In adjusted analyses, energy and total fat intakes were lower among those trying to lose weight compared to those never trying to lose weight. Intakes of cholesterol, sodium, and refined grains were not different by frequency of trying to lose weight (all p = 0.059-0.074). Weight loss efforts may be related to better nutritional profiles for some children and adolescents.

An in-home intervention of parent-implemented strategies to increase child vegetable intake: results from a non-randomized cluster-allocated community trial.

BACKGROUND: Less than 2% of children in the U.S., ages 9-13, meet the minimum dietary recommendations for vegetable intake. The home setting provides potential opportunities to promote dietary behavior change among children, yet limited trials exist with child vegetable intake as a primary outcome. Strategies to increase vegetable intake grounded in behavioral economics are no/low cost and may be easily implemented in the home by parents. METHODS: This non-randomized, controlled study tested whether an intervention of parent-led strategies informed by behavioral economics and implemented within a series of 6 weekly parent-child vegetable cooking skills classes, improved dietary outcomes of a diverse sample of low-income children (ages 9-12) more than the vegetable cooking skills classes alone. The primary outcomes were total vegetable intake, dietary quality (HEI scores), total energy intake, vegetable liking, variety of vegetables tried, child BMI-z score, and home availability of vegetables. Outcome measures were collected at baseline, immediate post-treatment, 6 and 12 months follow-up. Mixed model regression analyses with fixed independent effects (treatment condition, time point and treatment condition x time interaction) were used to compare outcomes between treatment conditions. RESULTS: A total of 103 parent/child pairs (intervention = 49, control = 54) were enrolled and 91 (intervention = 44, control = 47) completed the weekly cooking skills program. The intervention did not improve child total vegetable intake. Intervention children increased dark green vegetable intake from immediate post-treatment to 12 months. The number of vegetables children tried increased and mean vegetable liking decreased over time for both control and intervention children. CONCLUSIONS: Findings from this study suggest that the strategies and the manner in which they were implemented may not be effective in low-income populations. The burden of implementing a number of strategies with potentially higher food costs may have constrained the ability of families in the current study to use the strategies as intended. TRIAL REGISTRATION: This trial has been retrospectively registered at : # NCT03641521 on August 21, 2018.

Implementation of Parental Strategies to Improve Child Vegetable Intake: Barriers and Facilitators.

Purpose. To qualitatively assess barriers and facilitators to implementing specific behavioral strategies to increase child vegetable intake during home dinner meals by low-income parents. Method. Parents (n = 49) of children (9-12 years) were asked to implement 1 behavioral strategy following each of 6 weekly cooking classes at community centers. Example strategies included serving vegetables first, serving 2 vegetables, and using a bigger spoon to serve vegetables. The following week, parents discussed how they used the strategy and barriers and facilitators to its use. Discussions were recorded, transcribed verbatim, and coded separately by strategy using NVivo Pro 11 software. Inductive, comparative thematic analyses were used to identify themes by strategy. Results. Most participants were multiethnic women aged 30 to 39 years with low food security. Time and scheduling conflicts limited involvement of children in vegetable preparation (Child Help strategy). The type of foods served and an unfamiliar serving style inhibited use of the MyPlate and Available/Visible strategies, respectively. Children's dislike of vegetables limited use of the Serve Vegetables First and Serve 2 Vegetables strategies. Ease of use promoted use of the Bigger Spoon strategy. Conclusion. Educators could tailor application of specific parent strategies for low-income families based on child and environmental characteristics.

Children Residing in Low-Income Households Like a Variety of Vegetables.

Child vegetable intake falls far below the minimum recommended levels. Knowing which vegetables children may like help those responsible for providing vegetables to children to improve intake. The objective of this study was to measure vegetable liking for a wide variety of vegetables by a racially and ethnically diverse population of 9⁻12-year old children from low-income families. Children rated their liking of 35 vegetables using a 10-point hedonic scale. We tabulated the number of children that found each vegetable acceptable (ratings of 'okay' or above) and the number that found each vegetable unacceptable (ratings below 'okay'). More than 50% of children who had tried a vegetable considered it acceptable. A large majority of the vegetables had mean ratings in the acceptable range. Corn was the most liked vegetable, closely followed by potatoes, lettuce, and carrots. Artichoke had the lowest mean liking, followed by onion and beets. We found children liked a wide variety of vegetables which offers counter evidence to the commonly held perception that children do not like vegetables.

Impacts of a Vegetable Cooking Skills Program Among Low-Income Parents and Children.

OBJECTIVE: To evaluate the impact of a vegetable-focused cooking skills and nutrition program on parent and child psychosocial measures, vegetable liking, variety, and home availability. DESIGN: Baseline and postcourse surveys collected 1-week after the course. SETTING: Low-income communities in Minneapolis-St Paul. PARTICIPANTS: Parent-child dyads (n = 89; one third each Hispanic, African American, and white) with complete pre-post course data; flyer and e-mail recruitment. INTERVENTION(S): Six 2-hour-weekly sessions including demonstration, food preparation, nutrition education lessons, and a meal. MAIN OUTCOME MEASURES: Parental cooking confidence and barriers, food preparation/resource management, child self-efficacy and cooking attitudes, vegetable liking, vegetable variety, and vegetable home availability. ANALYSIS: Pre-post changes analyzed with paired t test or Wilcoxon signed-rank tests. Results were significant at P < .05. RESULTS: Increased parental cooking confidence (4.0 to 4.4/5.0), healthy food preparation (3.6 to 3.9/5.0), child self-efficacy (14.8 to 12.4; lower score = greater self-efficacy), vegetable variety (30 to 32/37 for parent, 22 to 24/37 for child), and home vegetable availability (16 to 18/35) (all P < .05). CONCLUSIONS AND IMPLICATIONS: A short-term evaluation of a vegetable-focused cooking and nutrition program for parents and children showed improvements in psychosocial factors, variety, and home availability.

Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans.

In infants exposed to maternal stress in utero, phenotypic plasticity through epigenetic events may mechanistically explain increased risk of preterm birth (PTB), which confers increased risk for neurodevelopmental disorders, cardiovascular disease, and cancers in adulthood. We examined associations between prenatal maternal stress and PTB, evaluating the role of DNA methylation at imprint regulatory regions. We enrolled women from prenatal clinics in Durham, NC. Stress was measured in 537 women at 12 weeks of gestation using the Perceived Stress Scale. DNA methylation at differentially methylated regions (DMRs) associated with H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 was measured from peripheral and cord blood using bisulfite pyrosequencing in a sub-sample of 79 mother-infant pairs. We examined associations between PTB and stress and evaluated differences in DNA methylation at each DMR by stress. Maternal stress was not associated with PTB (OR = 0.98; 95% CI, 0.40-2.40; P = 0.96), after adjustment for maternal body mass index (BMI), income, and raised blood pressure. However, elevated stress was associated with higher infant DNA methylation at the MEST DMR (2.8% difference, P < 0.01) after adjusting for PTB. Maternal stress may be associated with epigenetic changes at MEST, a gene relevant to maternal care and obesity. Reduced prenatal stress may support the epigenomic profile of a healthy infant.

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

PURPOSE: For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. METHODS: Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. RESULTS: Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. CONCLUSIONS: Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Erythrocyte folate concentrations, CpG methylation at genomically imprinted domains, and birth weight in a multiethnic newborn cohort.

Epigenetic mechanisms are proposed to link maternal concentrations of methyl group donor nutrients with the risk of low birth weight. However, empirical data are lacking. We have examined the association between maternal folate and birth weight and assessed the mediating role of DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes in these associations. Compared with newborns of women with folate levels in the lowest quartile, birth weight was higher in newborns of mothers in the second (ß = 143.2, se = 63.2, P = 0.02), third (ß = 117.3, se = 64.0, P = 0.07), and fourth (ß = 133.9, se = 65.2, P = 0.04) quartiles, consistent with a threshold effect. This pattern of association did not vary by race/ethnicity but was more apparent in newborns of non-obese women. DNA methylation at the PLAGL1, SGCE, DLK1/MEG3 and IGF2/H19 DMRs was associated with maternal folate levels and also birth weight, suggestive of threshold effects. MEG3 DMR methylation mediated the association between maternal folate levels and birth weight (P =0.06). While the small sample size and partial scope of examined DMRs limit our conclusions, our data suggest that, with respect to birth weight, no additional benefits may be derived from increased maternal folate concentrations, especially in non-obese women. These data also support epigenetic plasticity as a key mechanistic response to folate availability during early fetal development.

Maternal BMI, IGF-I Levels, and Birth Weight in African American and White Infants.

At birth, elevated IGF-I levels have been linked to birth weight extremes; high birth weight and low birth weight are risk factors for adult-onset chronic diseases including obesity, cardiovascular disease, and type 2 diabetes. We examined associations between plasma IGF-I levels and birth weight among infants born to African American and White obese and nonobese women. Prepregnancy weight and height were assessed among 251 pregnant women and anthropometric measurements of full term infants (≥37 weeks of gestation) were taken at birth. Circulating IGF-I was measured by ELISA in umbilical cord blood plasma. Linear regression models were utilized to examine associations between birth weight and high IGF-I, using the bottom two tertiles as referents. Compared with infants with lower IGF-I levels (≤3rd tertile), those with higher IGF-I levels (>3rd tertile) were 130 g heavier at birth, (ß-coefficient = 230, se = 58.0, P = 0.0001), after adjusting for gender, race/ethnicity, gestational age, delivery route, maternal BMI and smoking. Stratified analyses suggested that these associations are more pronounced in infants born to African American women and women with BMI ≥30 kg/m(2); the cross product term for IGF-I and maternal BMI was statistically significant (P ≤ 0.0004). Our findings suggest that the association between IGF-I levels and birth weight depends more on maternal obesity than African American race/ethnicity.

DNA methylation at imprint regulatory regions in preterm birth and infection.

OBJECTIVE: To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis). STUDY DESIGN: Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status. RESULTS: DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05. CONCLUSION: Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.

Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.