Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life.

BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. STUDY DESIGN: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated. RESULTS: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. CONCLUSION: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).

Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial.

IMPORTANCE: Preterm infants have immature respiratory control and resulting intermittent hypoxia (IH). The extent of IH after stopping routine caffeine treatment and the potential for reducing IH with extended caffeine treatment are unknown. OBJECTIVES: To determine (1) the frequency of IH in premature infants after discontinuation of routine caffeine treatment and (2) whether extending caffeine treatment to 40 weeks' postmenstrual age (PMA) reduces IH. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized clinical study was conducted at 16 neonatal intensive care units in the United States, with an 18-month enrollment period. Preterm infants (<32 weeks' gestation) previously treated with caffeine were randomized to extended caffeine treatment or usual care (controls) at a PMA of at least 34 weeks but less than 37 weeks. Continuous pulse oximeter recordings were obtained through 40 weeks' PMA. Oximeter data were analyzed by persons masked to patient group. INTERVENTION: Continued treatment with caffeine. MAIN OUTCOMES AND MEASURES: Number of IH events and seconds with less than 90% hemoglobin oxygen saturation (Sao2) per hour of recording. RESULTS: Our analysis included 95 preterm infants. In control infants, the mean (SD) time at less than 90% Sao2 at 35 and 36 weeks' PMA was 106.3 (89.0) and 100.1 (114.6) s/h, respectively. The number of IH events decreased significantly from 35 to 39 weeks' PMA (P = .01). Extended caffeine treatment reduced the mean time at less than 90% Sao2 by 47% (95% CI, -65% to -20%) to 50.9 (48.1) s/h at 35 weeks and by 45% (95% CI, -74% to -17%) to 49.5 (52.1) s/h at 36 weeks. CONCLUSIONS AND RELEVANCE: Substantial IH persists after discontinuation of routine caffeine treatment and progressively decreases with increasing PMA. Extended caffeine treatment decreases IH in premature infants. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01875159.

Child food insecurity increases risks posed by household food insecurity to young children's health.

The US Food Security Scale (USFSS) measures household and child food insecurity (CFI) separately. Our goal was to determine whether CFI increases risks posed by household food insecurity (HFI) to child health and whether the Food Stamp Program (FSP) modifies these effects. From 1998 to 2004, 17,158 caregivers of children ages 36 mo were interviewed in six urban medical centers. Interviews included demographics, the USFSS, child health status, and hospitalization history. Ten percent reported HFI, 12% HFI and CFI (H&CFI). Compared with food-secure children, those with HFI had significantly greater adjusted odds of fair/poor health and being hospitalized since birth, and those with H&CFI had even greater adverse effects. Participation in the FSP modified the effects of FI on child health status and hospitalizations, reducing, but not eliminating, them. Children in FSP-participating households that were HFI had lower adjusted odds of fair/poor health [1.37 (95% CI, 1.06-1.77)] than children in similar non-FSP households [1.61 (95% CI, 1.31-1.98)]. Children in FSP-participating households that were H&CFI also had lower adjusted odds of fair/poor health [1.72 (95% CI, 1.34-2.21)] than in similar non-FSP households [2.14 (95% CI, 1.81-2.54)]. HFI is positively associated with fair/poor health and hospitalizations in young children. With H&CFI, odds of fair/poor health and hospitalizations are even greater. Participation in FSP reduces, but does not eliminate, effects of FI on fair/poor health.

Use of self-report to predict ability to walk 400 meters in mobility-limited older adults.

OBJECTIVES: To determine whether the ability to walk 400 m could be predicted from self-reported walking habits and abilities in older adults and to develop an accurate self-report measure appropriate for observational trials of mobility when functional measures are impractical to collect. DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred fifty community-dwelling older men and women (mean age+/-standard error= 79.8+/-0.3). MEASUREMENTS: An 18-item questionnaire assessing walking habits and ability was administered to each participant, followed by a 400-m walk test. Ninety-eight (65%) volunteers were able to complete the 400-m walk; 52 (35%) were unable. Logistic regression was performed using response items from a questionnaire as predictors and 400-m walk as the outcome. RESULTS: Three questions (Do you think you could walk one-quarter of a mile now without sitting down to rest. Because of a health or physical problem, do you have difficulty walking 1 mile? Could you walk up and down every aisle of a grocery store without sitting down to rest or leaning on a cart?) were predictive of 400-m walking ability and were included in the model. If participants answered all three questions compatible with the inability to walk 400 m, there was a 91% probability that they were unable to walk 400 m, with a sensitivity of 46% and a specificity of 97%. CONCLUSION: A three-item self-report developed in the study was able to accurately predict mobility disability. The utility of this instrument may be in evaluating self-reported mobility in large observational trials on mobility when functional mobility tasks are impractical to collect.

Alcohol consumption and the prevalence of the Metabolic Syndrome in the US.: a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey.

OBJECTIVE: The aim of this study was to examine the relations of alcohol consumption to the prevalence of the metabolic syndrome and its components in the U.S. population. RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis on data from 8,125 participants from the Third National Health and Nutrition Examination Survey who were evaluated for each component of the metabolic syndrome, using the National Cholesterol Education Program criteria, fasting insulin, and alcohol consumption. Current alcohol consumption was defined as > or =1 alcoholic drink per month. RESULTS: After adjustment for age, sex, race/ethnicity, education, income, tobacco use, physical activity, and diet, subjects who consumed 1-19 and > or =20 drinks of alcohol per month had odds ratios (ORs) for the prevalence of the metabolic syndrome of 0.65 and 0.34, respectively (P <0.05 for all), compared with current nondrinkers. These findings were particularly noteworthy for beer and wine drinkers. The association of > or =20 alcoholic drinks per month with the prevalence of the metabolic syndrome was consistent across ethnicities but was most striking in white men and women (ORs 0.35 and 0.22, respectively; P <0.05). Alcohol consumption was significantly and inversely associated with the prevalence of the following three components of the metabolic syndrome: low serum HDL cholesterol, elevated serum triglycerides, high waist circumference, as well as hyperinsulinemia (P <0.05 for all). CONCLUSIONS: Mild to moderate alcohol consumption is associated with a lower prevalence of the metabolic syndrome, with a favorable influence on lipids, waist circumference, and fasting insulin. This association was strongest among whites and among beer and wine drinkers.

Validation of the Late-Life Function and Disability Instrument.

OBJECTIVES: To assess the concurrent and predictive validity of the Late-Life Function and Disability Instrument (LLFDI). DESIGN: Cross-sectional. SETTING: University-based human physiology laboratory. PARTICIPANTS: One hundred one men and women aged 80.8 +/- 0.4. MEASUREMENTS: A short physical performance battery (SPPB) and a self-paced 400-m walk (400-m W) were used as performance tests of lower extremity function. The LLFDI was used to assess self-reported function and physical disability. Partial correlations adjusted for age and body mass index were used to determine the concurrent and predictive validity of the LLFDI. Statistical significance was accepted at P<.004 using a testwise correction. RESULTS: LLFDI Overall Function scores were moderately associated with the SPPB (r=0.65, P<.001), 400-m W gait speed (r=0.69, P<.001), and measures of lower extremity function. Correlations of the two lower extremity subscores of the LLFDI (correlation coefficient (r)=0.63-0.73, P<.001) were greater than for the LLFDI upper extremity subscores (r=0.19-0.26, P>.004). Performance measures of function predicted disability limitations in the range of r=0.37-0.44 (P<.001) and disability frequency in the range of r=0.16-0.20 (P>.004). CONCLUSION: These findings support the concurrent and predictive validity of the LLFDI. Results support the use of the LLFDI scales as a substitute for physical performance tests when self-report is a preferred data-collection format.