Off the Charts: Identifying and Visualizing Body Mass Index Trajectories of Rural, Poor Youth.

OBJECTIVES: To identify body mass index (BMI) trajectories using methods and graphing tools that maintain and visualize variability of BMIs ≥95th percentile, and to investigate individual differences in early sociodemographic risk, infant growth and feeding patterns, and maternal weight status among these trajectories. STUDY DESIGN: Participants included 1041 predominantly rural, poor families from the Family Life Project, a longitudinal birth cohort. Youth anthropometrics were measured 8 times between ages 2 months and 12 years. Mothers reported sociodemographic information, infant birth weight, and infant feeding at 2 months and reported child weight and height at 2 months and 12 years. At 6 months, mothers reported breastfeeding. At 2 years, maternal weight and height were measured. RESULTS: Three BMI trajectories were identified: "maintained non-overweight," "developed obesity," and "developed severe obesity." Compared with the non-overweight trajectory, children with heavier trajectories were breastfed for a shorter duration and had heavier mothers at all assessments. The children with the "developed obesity" trajectory were not heavier at birth than those with the non-overweight trajectory, yet they displayed a greater change in weight-for-length percentile during infancy; in addition, their mothers had the greatest change in BMI between 2 months and 12 years. Children with the "developed severe obesity" trajectory were heavier at birth and more likely to have been heavy during infancy and to have been fed solid foods early. CONCLUSIONS: Using informed analytical and graphing approaches, we described patterns of growth, and identified early predictors of obesity and severe obesity trajectories among a diverse sample of rural, poor youth. Researchers are urged to consider these approaches in future work, and to focus on identifying protective factors in youth with obesity and severe obesity.

Maternal controlling feeding practices and girls' inhibitory control interact to predict changes in BMI and eating in the absence of hunger from 5 to 7 y.

BACKGROUND: Mothers use a range of feeding practices to limit children's intake of palatable snacks (eg, keeping snacks out of reach, not bringing snacks into the home), but less is known about the effects of these practices on children's eating and weight outcomes. OBJECTIVE: The objective was to identify distinct feeding practice profiles and evaluate the interactive effects of these profiles and girls' temperament (inhibitory control and approach) on girls' eating behaviors and weight outcomes at 5 and 7 y. DESIGN: Participants included 180 mother-daughter dyads; measures were mothers' reports of controlling feeding practices and girls' height and weight, eating in the absence of hunger (EAH) at 5 y, and inhibitory control (a measure of behavioral inhibition) and approach (a measure of appetitive motivation) at 7 y. RESULTS: Latent profile analysis of maternal feeding practices showed 4 feeding profiles based on maternal use of limit-setting practices and keeping snacks out of girls' physical reach, a restrictive practice: Unlimited Access to Snacks, Sets Limits+Does Not Restrict Snacks, Sets Limits+Restricts High Fat/Sugar Snacks, and Sets Limits+Restricts All Snacks. Girls whose mothers used Sets Limits+Restricts All Snacks had a higher approach and EAH at 5 y. Low inhibitory control girls whose mothers used Sets Limits+Restricts All Snacks or Unlimited Access to Snacks had greater increases in EAH and body mass index (BMI) from 5 to 7 y. CONCLUSIONS: Effects of maternal control on girls' EAH and BMI may differ by the type of practice used (eg, limit-setting or restrictive practices). Girls with low inhibitory control were more susceptible to the negative effects of low and high control.

Evidence of allelic imbalance in the schizophrenia susceptibility gene ZNF804A in human dorsolateral prefrontal cortex.

The rs1344706, an intronic SNP within the zinc-finger protein 804A gene (ZNF804A), was identified as one of the most compelling risk SNPs for schizophrenia (SZ) and bipolar disorder (BD). It is however not clear by which molecular mechanisms ZNF804A increases disease risk. We evaluated the role of ZNF804A in SZ and BD by genotyping the originally associated rs1344706 SNP and an exonic SNP (rs12476147) located in exon four of ZNF804A in a sample of 422 SZ, 382 BD, and 507 controls from the isolated population of the Costa Rica Central Valley. We also investigated the rs1344706 SNP for allelic specific expression (ASE) imbalance in the dorsolateral prefrontal cortex (DLPFC) of 46 heterozygous postmortem brains. While no significant association between rs1344706 and SZ or BD was observed in the Costa Rica sample, we observed an increased risk of SZ for the minor allele (A) of the exonic rs12476147 SNP (p=0.026). Our ASE assay detected a significant over-expression of the rs12476147 A allele in DLPFC of rs1344706 heterozygous subjects. Interestingly, cDNA allele ratios were significantly different according to the intronic rs1344706 genotypes (p-value=0.03), with the rs1344706 A allele associated with increased ZNF804A rs12476147 A allele expression (average 1.06, p-value=0.02, for heterozygous subjects vs. genomic DNA). In conclusion, we have demonstrated a significant association of rs12476147 with SZ, and using a powerful within-subject design, an allelic expression imbalance of ZNF804A exonic SNP rs12476147 in the DLPFC. Although this data does not preclude the possibility of other functional variants in ZNF804A, it provides evidence that the rs1344706 SZ risk allele is the cis-regulatory variant directly responsible for this allelic expression imbalance in adult cortex.

Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.

A missense polymorphism in the NRG1 gene, Val>Leu in exon 11, was reported to increase the risk of schizophrenia in selected families from the Central Valley region of Costa Rica (CVCR). The present study investigated the relationship between three NRG1 genetic variants, rs6994992, rs3924999, and Val>Leu missense polymorphism in exon 11, in cases and selected controls from an isolated population from the CVCR. Isolated populations can have less genetic heterogeneity and increase power to detect risk variants in candidate genes. Subjects with bipolar disorder (BD, n=358), schizophrenia (SZ, n=273), or unrelated controls (CO, n=479) were genotyped for three NRG1 variants. The NRG1 promoter polymorphism (rs6994992) was related to altered expression of NRG1 Type IV in other studies. The expression of NRG1 type IV in the dorsolateral prefrontal cortex (DLPFC) and the effect of the rs6994992 genotype on expression were explored in a postmortem cohort of BD, SZ, major depressive disorder (MDD) cases, and controls. The missense polymorphism Val>Leu in exon 11 was not significantly associated with schizophrenia as previously reported in a family sample from this population, the minor allele frequency is 4%, thus our sample size is not large enough to detect an association. We observed however an association of rs6994992 with NRG1 type IV expression in DLPFC and a significantly decreased expression in MDD compared to controls. The present results while negative do not rule out a genetic association of these SNPs with BD and SZ in CVCR, perhaps due to small risk effects that we were unable to detect and potential intergenic epistasis. The previous genetic relationship between expression of a putative brain-specific isoform of NRG1 type IV and SNP variation was replicated in postmortem samples in our preliminary study.

HIV prevention costs and program scale: data from the PANCEA project in five low and middle-income countries.

BACKGROUND: Economic theory and limited empirical data suggest that costs per unit of HIV prevention program output (unit costs) will initially decrease as small programs expand. Unit costs may then reach a nadir and start to increase if expansion continues beyond the economically optimal size. Information on the relationship between scale and unit costs is critical to project the cost of global HIV prevention efforts and to allocate prevention resources efficiently. METHODS: The "Prevent AIDS: Network for Cost-Effectiveness Analysis" (PANCEA) project collected 2003 and 2004 cost and output data from 206 HIV prevention programs of six types in five countries. The association between scale and efficiency for each intervention type was examined for each country. Our team characterized the direction, shape, and strength of this association by fitting bivariate regression lines to scatter plots of output levels and unit costs. We chose the regression forms with the highest explanatory power (R2). RESULTS: Efficiency increased with scale, across all countries and interventions. This association varied within intervention and within country, in terms of the range in scale and efficiency, the best fitting regression form, and the slope of the regression. The fraction of variation in efficiency explained by scale ranged from 26-96%. Doubling in scale resulted in reductions in unit costs averaging 34.2% (ranging from 2.4% to 58.0%). Two regression trends, in India, suggested an inflection point beyond which unit costs increased. CONCLUSION: Unit costs decrease with scale across a wide range of service types and volumes. These country and intervention-specific findings can inform projections of the global cost of scaling up HIV prevention efforts.