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1. Cesarean birth and the growth of Yucatec Maya and Toba/Qom children

   https://doi.org/10.1002/ajhb.23228  

   Veile, Amanda ; Valeggia, Claudia ; Kramer, Karen L. ( February 2019 , American Journal of Human Biology)

   Cesarean delivery is often epidemiologically associated with childhood obesity. However, little attention is paid to post‐birth modulatory environments, and most studies are conducted in settings where obesity arises for a number of reasons in addition to birth mode. We therefore assess population differences in the relationship between birth mode and childhood growth using data from rural and peri‐urban Latin American indigenous populations, and test predictions developed using life history theory.

   Child height and weight were measured monthly in 80 Yucatec Maya and 58 Toba/Qom children aged 1‐48 months (2007‐2014, 3812 observations). Random‐effects linear mixed models were used to compare children's growth by population, sex, and birth mode, accounting for potential confounders.

   Cesarean delivery rates were 47% (Toba/Qom) and 20% (Yucatec Maya). Childhood obesity and overweight rates were low in both populations. Cesarean‐delivered children had significantly greater weight gain (but similar height grain) compared to vaginally‐delivered children. By age 4, cesarean delivered Yucatec Maya girls and boys, and Toba/Qom boys (not girls), had significantly higher weight‐for‐age compared to vaginally‐delivered children from their own sex and population.

   This provides one of the first attempts to document differences in children's growth patterns according to mode of birth in modernizing indigenous populations. Cesarean delivery is associated with young children's growth patterns, even in the absence of many obesity‐inducing factors. There are also population, age, and sex differences in the relationship between birth mode and childhood weight trajectories that warrant future investigation.

    

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2. FTO variation and early frontostriatal brain development in children

   https://doi.org/10.1002/oby.23926  

   Thapaliya, Gita ; Kundu, Poorbita ; Jansen, Elena ; Naymik, Marcus A. ; Lee, Richard ; Bruchhage, Muriel Marisa Katharina ; D'Sa, Viren ; Huentelman, Matthew J. ; Lewis, Candace R. ; Müller, Hans‐Georg ; et al ( October 2023 , Obesity)

   Common obesity‐associated genetic variants at the fat mass and obesity‐associated (FTO) locus have been associated with appetitive behaviors and altered structure and function of frontostriatal brain regions. The authors aimed to investigate the influence ofFTOvariation on frontostriatal appetite circuits in early life.

   Data were drawn from RESONANCE, a longitudinal study of early brain development. Growth trajectories of nucleus accumbens and frontal lobe volumes, as well as total gray matter and white matter volume, by risk allele (AA) carrier status onFTOsingle‐nucleotide polymorphism rs9939609 were examined in 228 children (102 female, 126 male) using magnetic resonance imaging assessments obtained from infancy through middle childhood. The authors fit functional concurrent regression models with brain volume outcomes over age as functional responses, andFTOgenotype, sex, BMIzscore, and maternal education were included as predictors.

   Bootstrap pointwise 95% CI for regression coefficient functions in the functional concurrent regression models showed that the AA group versus the group with no risk allele (TT) had greater nucleus accumbens volume (adjusted for total brain volume) in the interval of 750 to 2250 days (2–6 years).

   These findings suggest that common genetic risk for obesity is associated with differences in early development of brain reward circuitry and argue for investigating dynamic relationships among genotype, brain, behavior, and weight throughout development.

    

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3. Childhood body mass is positively associated with cesarean birth in Y ucatec M aya subsistence farmers

   https://doi.org/10.1002/ajhb.22920  

   Veile, Amanda ; Kramer, Karen L. ( October 2016 , American Journal of Human Biology)

   The epidemiologic link between cesarean birth and childhood obesity is unresolved, partly because most studies come from industrialized settings where many post‐birth factors affect the risk for obesity. We take advantage of an unusual ethnographic situation where hospital and cesarean birth modes have recently been introduced among Yucatec Maya subsistence farmers, but young children have had minimal exposure to the nutritional transition. While we expect to find very low rates of childhood obesity, we predict that cesarean‐born children will be larger and heavier than vaginally born children.

   Weight and height were collected monthly on 108 children aged 0–5 (3576 observations total). Birth mode and birthweight were collected by maternal interview. Data were analyzed using linear mixed models that compare child growth [Maya population‐specificZ‐scores for weight‐for‐age and body mass index‐for‐age (WAZ and BMIZ)] in cesarean and vaginally born children aged 0–5 years.

   The cesarean rate was 20%, no children were obese, and 5% were overweight. Cesarean birth was a significant predictor of child WAZ and BMIZ after accounting for maternal effects, child birthweight, and sex. Children who were born by cesarean to mothers with high BMI had the highest WAZ of all children by 5 years of age, and the highest BMIZ of all children at all ages.

   Cesarean‐born Maya children had higher BMI than vaginally born children, even in the absence of many known confounding factors that contribute to childhood obesity. Child growth was most sensitive to birth mode when mothers had high BMI.

    

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4. Disparities in Hemoglobin A 1c Levels in the First Year After Diagnosis Among Youths With Type 1 Diabetes Offered Continuous Glucose Monitoring

   https://doi.org/10.1001/jamanetworkopen.2023.8881  

   Addala, Ananta ; Ding, Victoria ; Zaharieva, Dessi P. ; Bishop, Franziska K. ; Adams, Alyce S. ; King, Abby C. ; Johari, Ramesh ; Scheinker, David ; Hood, Korey K. ; Desai, Manisha ; et al ( April 2023 , JAMA Network Open)

   Importance Continuous glucose monitoring (CGM) is associated with improvements in hemoglobin A 1c (HbA 1c ) in youths with type 1 diabetes (T1D); however, youths from minoritized racial and ethnic groups and those with public insurance face greater barriers to CGM access. Early initiation of and access to CGM may reduce disparities in CGM uptake and improve diabetes outcomes. Objective To determine whether HbA 1c decreases differed by ethnicity and insurance status among a cohort of youths newly diagnosed with T1D and provided CGM. Design, Setting, and Participants This cohort study used data from the Teamwork, Targets, Technology, and Tight Control (4T) study, a clinical research program that aims to initiate CGM within 1 month of T1D diagnosis. All youths with new-onset T1D diagnosed between July 25, 2018, and June 15, 2020, at Stanford Children’s Hospital, a single-site, freestanding children’s hospital in California, were approached to enroll in the Pilot-4T study and were followed for 12 months. Data analysis was performed and completed on June 3, 2022. Exposures All eligible participants were offered CGM within 1 month of diabetes diagnosis. Main Outcomes and Measures To assess HbA 1c change over the study period, analyses were stratified by ethnicity (Hispanic vs non-Hispanic) or insurance status (public vs private) to compare the Pilot-4T cohort with a historical cohort of 272 youths diagnosed with T1D between June 1, 2014, and December 28, 2016. Results The Pilot-4T cohort comprised 135 youths, with a median age of 9.7 years (IQR, 6.8-12.7 years) at diagnosis. There were 71 boys (52.6%) and 64 girls (47.4%). Based on self-report, participants’ race was categorized as Asian or Pacific Islander (19 [14.1%]), White (62 [45.9%]), or other race (39 [28.9%]); race was missing or not reported for 15 participants (11.1%). Participants also self-reported their ethnicity as Hispanic (29 [21.5%]) or non-Hispanic (92 [68.1%]). A total of 104 participants (77.0%) had private insurance and 31 (23.0%) had public insurance. Compared with the historical cohort, similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were observed for Hispanic individuals (estimated difference, −0.26% [95% CI, −1.05% to 0.43%], −0.60% [−1.46% to 0.21%], and −0.15% [−1.48% to 0.80%]) and non-Hispanic individuals (estimated difference, −0.27% [95% CI, −0.62% to 0.10%], −0.50% [−0.81% to −0.11%], and −0.47% [−0.91% to 0.06%]) in the Pilot-4T cohort. Similar reductions in HbA 1c at 6, 9, and 12 months postdiagnosis were also observed for publicly insured individuals (estimated difference, −0.52% [95% CI, −1.22% to 0.15%], −0.38% [−1.26% to 0.33%], and −0.57% [−2.08% to 0.74%]) and privately insured individuals (estimated difference, −0.34% [95% CI, −0.67% to 0.03%], −0.57% [−0.85% to −0.26%], and −0.43% [−0.85% to 0.01%]) in the Pilot-4T cohort. Hispanic youths in the Pilot-4T cohort had higher HbA 1c at 6, 9, and 12 months postdiagnosis than non-Hispanic youths (estimated difference, 0.28% [95% CI, −0.46% to 0.86%], 0.63% [0.02% to 1.20%], and 1.39% [0.37% to 1.96%]), as did publicly insured youths compared with privately insured youths (estimated difference, 0.39% [95% CI, −0.23% to 0.99%], 0.95% [0.28% to 1.45%], and 1.16% [−0.09% to 2.13%]). Conclusions and Relevance The findings of this cohort study suggest that CGM initiation soon after diagnosis is associated with similar improvements in HbA 1c for Hispanic and non-Hispanic youths as well as for publicly and privately insured youths. These results further suggest that equitable access to CGM soon after T1D diagnosis may be a first step to improve HbA 1c for all youths but is unlikely to eliminate disparities entirely. Trial Registration ClinicalTrials.gov Identifier: NCT04336969 

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5. Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity

   https://doi.org/10.3390/genes13112030  

   Patel, Priyadarshni ; Selvaraju, Vaithinathan ; Babu, Jeganathan Ramesh ; Wang, Xu ; Geetha, Thangiah ( November 2022 , Genes)

   Childhood obesity has affected the health of millions of children around the world despite vigorous efforts by health experts. The obesity epidemic in the United States has disproportionately afflicted certain racial and ethnic minority groups. African American children are more likely than other children to have obesity-related risk factors such as hyperlipidemia, diabetes, cardiovascular disease, and coronavirus disease (COVID-19). For the reduction in obesity-related health inequalities to be successful, it is essential to identify the variables affecting various groups. A notable advancement in epigenetic biology has been made over the past decade. Epigenetic changes like DNA methylation impact on many genes associated with obesity. Here, we evaluated the DNA methylation levels of the genes NRF1, FTO, and LEPR from the saliva of children using real-time quantitative PCR-based multiplex MethyLight technology. ALU was used as a reference gene, and the Percent of Methylated Reference (PMR) was calculated for each sample. European American children showed a significant increase in PMR of NRF1 and FTO in overweight/obese participants compared to normal weight, but not in African American children. After adjusting for maternal education and annual family income by regression analysis, the PMR of NRF1 and FTO was significantly associated with BMI z-score only in European American children. While for the gene LEPR, African American children had higher methylation in normal weight participants as compared to overweight/obese and no methylation difference in European American children. The PMR of LEPR was significantly negative associated with the obesity measures only in African American children. These findings contribute to a race-specific link between NRF1, FTO, and LEPR gene methylation and childhood obesity. 

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