Z-score Units Research Articles

Life Course Socioeconomic Position and Cognitive Aging Trajectories: A Cross-National Cohort Study in China and England.

Cross-national research on cognitive aging inequality has largely concentrated on Western countries. It is unclear whether socioeconomic position (SEP) has similar effects on cognitive decline in emerging economies. We compared the association between life course SEP and cognitive function trajectories between China and England, the largest nation under state socialism and one of the oldest capitalist countries. This cross-cohort study examined participants aged 50 years and older from the China Health and Retirement Longitudinal Study (n = 12,832) and the English Longitudinal Study of aging (n = 8,875). Cognition z-scores were derived using comparable measures of memory and time orientation on 4 occasions. Life course SEP was self-reported by participants at baseline. Seven- to 8-year trajectories of cognition z-scores were estimated using latent growth curve modeling. Country- and gender-specific associations between childhood/adolescent deprivation, education, material wealth, and home ownership were evaluated in relation to model intercept (baseline level) and linear slope (annual rate of change) of cognition. After multivariable adjustment, education was positively associated with the greatest differences in baseline cognition across country and gender. Education was further linked to a slower rate of cognitive decline (z-score units per year); but compared with those with low education, Chinese men (b = 0.032) and women (b = 0.065) with high education had significantly slower declines than English men (b = -0.004) and women (b = 0.010) with high education. Despite substantial between-cohort differences in downstream and upstream determinants of dementia, education provided the greatest benefits to cognitive aging in England but particularly in China.

Perinatal Outcomes during versus Prior to the COVID-19 Pandemic and the Role of Maternal Depression and Perceived Stress: A Report from the ECHO Program.

We sought to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on perinatal outcomes while accounting for maternal depression or perceived stress and to describe COVID-specific stressors, including changes in prenatal care, across specific time periods of the pandemic. Data of dyads from 41 cohorts from the National Institutes of Health Environmental influences on Child Health Outcomes Program (N = 2,983) were used to compare birth outcomes before and during the pandemic (n = 2,355), and a partially overlapping sample (n = 1,490) responded to a COVID-19 questionnaire. Psychosocial stress was defined using prenatal screening for depression and perceived stress. Propensity-score matching and general estimating equations with robust variance estimation were used to estimate the pandemic's effect on birth outcomes. Symptoms of depression and perceived stress during pregnancy were similar prior to and during the pandemic, with nearly 40% of participants reporting mild to severe stress, and 24% reporting mild depression to severe depression. Gestations were shorter during the pandemic (B = - 0.33 weeks, p = 0.025), and depression was significantly associated with shortened gestation (B = - 0.02 weeks, p = 0.015) after adjustment. Birth weights were similar (B = - 28.14 g, p = 0.568), but infants born during the pandemic had slightly larger birth weights for gestational age at delivery than those born before the pandemic (B = 0.15 z-score units, p = 0.041). More women who gave birth early in the pandemic reported being moderately or extremely distressed about changes to their prenatal care and delivery (45%) compared with those who delivered later in the pandemic. A majority (72%) reported somewhat to extremely negative views of the impact of COVID-19 on their life. In this national cohort, we detected no effect of COVID-19 on prenatal depression or perceived stress. However, experiencing the COVID-19 pandemic in pregnancy was associated with decreases in gestational age at birth, as well as distress about changes in prenatal care early in the pandemic. · COVID-19 was associated with shortened gestations.. · Depression was associated with shortened gestations.. · However, stress during the pandemic remained unchanged.. · Most women reported negative impacts of the pandemic..

ODP277 Urinary Concentrations of Polycyclic Aromatic Hydrocarbons and Childhood Obesity

Abstract Background Polycyclic aromatic hydrocarbons (PAHs), primarily produced by incomplete combustion of organic materials, have been suggested as obesogens, but information on PAHs and obesity, especially in children, is limited. We examined the cross-sectional association between urinary concentrations of PAHs and obesity in the Korean pediatric population. Methods We analyzed the data of 2286 children and adolescents aged 3–17 years who participated in the Korean National Environmental Health Survey (KoNEHS) 2015–2017. Urinary concentrations of 2-naphthol, 2-hydroxyfluorene, 1-hydroxyphenanthrene, and 1-hydroxypyrene were assayed using gas chromatography-mass spectrometry. Covariate-adjusted standardization method was used for the urinary dilution adjustment. Overweight and obesity were defined as BMI-for-age ≥85th percentile and ≥95th percentile, respectively. Multiple linear and logistic regression models were performed to analyze the relationship of BMI z-score and overweight with urinary concentrations of PAHs after adjusting for age, sex, household income, parental education level, physical activity, fast-food consumption, and ETS exposure. Results Obese children showed significantly higher urinary 2-naphthol concentrations than normal-weighted children in the overall population [3.62 µg/L (95% confidence intervals (95% CI): 3.20, 4. 09) vs. 2.88 µg/L (95% CI: 2.62, 3.16)]. Similar findings were observed in the age groups 6-11 and 12-17 years. Significant increases in BMI z-scores for 10 times increase in urinary 2-naphthol concentrations were observed in the age groups 6-11 [0.31 z-score units, (95% CI: 0.13, 0.49), P = 0. 001] and 12-17 years [0.33 z-score units, (95% CI: 0. 05, 0.60), P=0. 02]. A significant but smaller association was observed between change in BMI z-score and 1-hydroxypyrene concentrations in the 6-11 year group [0.14 z-score units, (95% CI: 0. 02, 0.27), P=0. 03]. The multiple logistic regression models for overweight showed significant positive associations with the quartiles of 2-NAP in the overall population [OR (95% CI); 1.14 (0.83-1.55), 1.39 (1. 03, 1.88), 1.46 (1. 08, 1.99) in the 2nd, 3rd, and 4th quartile, respectively, compared with the 1st quartile; P-for-trend=0. 006]. Similar associations between 2-naphthol and overweight status were also observed in the 6-11 year and 12-17 year groups. Conclusion This result suggests a possible link between PAH exposure, particularly 2-naphthol, and obesity in the Korean pediatric population. Given the growing obesity rates among Asian children and adolescents, this finding warrants further studies on the impacts of long-term exposure of PAHs on childhood obesity and possible mechanisms for this association. Presentation: No date and time listed

Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy

Preservation of photoreceptors beyond areas of retinal pigment epithelium atrophy is a critical treatment goal in eyes with geographic atrophy (GA) to prevent vision loss. Thus, we assessed the association of treatment with the complement C3 inhibitor pegcetacoplan with optical coherence tomography (OCT)-based photoreceptor laminae thicknesses in this post hoc analysis of the FILLY trial (NCT02503332). Retinal layers in OCT were segmented using a deep-learning-based pipeline and extracted along evenly spaced contour-lines surrounding areas of GA. The primary outcome measure was change from baseline in (standardized) outer nuclear layer (ONL) thickness at the 5.16°-contour-line at month 12. Participants treated with pegcetacoplan monthly had a thicker ONL along the 5.16° contour-line compared to the pooled sham arm (mean difference [95% CI] + 0.29 z-score units [0.16, 0.42], P < 0.001). The same was evident for eyes treated with pegcetacoplan every other month (+ 0.26 z-score units [0.13, 0.4], P < 0.001). Additionally, eyes treated with pegcetacoplan exhibited a thicker photoreceptor inner segment layer along the 5.16°-contour-line at month 12. These findings suggest that pegcetacoplan could slow GA progression and lead to reduced thinning of photoreceptor layers beyond the GA boundary. Future trials in earlier disease stages, i.e., intermediate AMD, aiming to slow photoreceptor degeneration warrant consideration.

Effect of an interactive mobile health support system and daily weight measurements for pediatric obesity treatment, a 1-year pragmatical clinical trial

BackgroundPediatric obesity lifestyle treatment is not always successful. Frequent clinical visits are of major importance to certify sufficient effect but are difficult due to the associated costs and the great demands on families. We hypothesized that an interactive digital support may reduce the need for frequent physical visits. The aim of the study was to assess 1-year weight outcome for patients using a digital support system compared with standard care.MethodsAn obesity lifestyle treatment with a digital support system was implemented in one clinic in Stockholm, Sweden. Measurements from a custom-made body scale without digits for daily home measurement of weights were transferred via Bluetooth to a mobile application, where BMI Z-score was calculated and presented graphically with an individualized weight loss target curve. An automatic transfer of data to the web-based clinic interface enables a close monitoring of treatment progress, and frequent written communication between the clinical staff and families via the application. One-year outcome was compared with a randomly retrieved, age and sex matched control group from the Swedish childhood obesity treatment register (BORIS), which received standard treatment at other clinics. Main outcome was change in BMI Z-score and missing data was imputed.Results107 children were consecutively included to digi-physical treatment and 321 children to standard care. Age range 4.1–17.4 years (67% males). The attrition rate was 36% and 46% respectively, p = 0.08. After 1 year, the mean ± SD change in BMI Z-score in the treatment group was −0.30 ± 0.39 BMI Z-score units and in the standard care group −0.15 ± 0.28, p = 0.0002. The outcome was better for both sexes and all age groups in the digi-physical treated group.ConclusionA digital support system with a personalized weight-loss target curve and daily weight measurements shared by the family and the clinic is more effective than a standard care childhood obesity treatment.Clinicaltrial.gov IDNCT04323215

Bone mineral density in very low birthweight adults-A sibling study.

BackgroundChildren and adults born very low birthweight (VLBW, <1500 g) at preterm gestations have lower bone mineral density (BMD) and/or bone mineral content (BMC) than those born at term, but causality remains unknown.ObjectivesOur aim was to assess BMD and BMC in adults born at VLBW in a sibling comparison setting to account for shared genetic and environmental confounders.MethodsWe conducted a cohort study of 77 adults born VLBW and 70 same‐sex term‐born siblings at mean age of 29 years. The primary outcome variables were BMD Z‐scores, and BMC, of the femoral neck, lumbar spine, and whole body, measured using dual‐energy X‐ray absorptiometry. We analysed data by linear mixed models.ResultsThe VLBW adults had a 0.25 (95% CI 0.02, 0.47) Z‐score unit lower femoral neck BMD, and 0.35 (95% CI 0.16, 0.54) grams lower femoral neck BMC than their term‐born siblings, after adjustment for sex, age, and maternal smoking. Additional adjustment for adult body size attenuated the results. Lumbar spine, and whole body BMC were also lower in the VLBW group.ConclusionsIndividuals born at VLBW had lower BMC values at all three measurement sites, as well as lower femoral neck BMD Z‐scores, compared to term‐born siblings, partly explained by their smaller adult body size, but the differences were smaller than those reported previously with unrelated controls. This suggests that genetic or environmental confounders explain partly, but not exclusively, the association between preterm VLBW birth and adult bone mineralisation.

Abstract P081: Rethinking The Association Of Physical Performance With Blood Pressure Changes In Older Women: Findings Form The Women’S Health Initiative

Rethinking the Association of Physical Performance with Blood Pressure Changes in Older Women: Findings form the Women’s Health Initiative Background: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods: 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65-69 y; 70-79 y). Results: Overall, each z-score unit increment in grip strength was associated with 0.54 mmHg (95% CI 0.06, 1.03) higher SBP, and 0.34 mmHg (95% CI 0.07, 0.62) higher DBP ( Table 1 ). In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.74; 95% CI 0.16-1.32), among antihypertensive medication users (0.89; 95% CI 0.41, 1.37) and non-users (0.35; 95% CI 0.01, 0.68), and in those aged 65-69 y (0.64; 95% CI 0.04, 1.23). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70-79 y. Associations between any performance measure and pulse pressure change were not significant. Conclusion: These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age. Total characters with table: 2,213 Table 1:

School starting age and nutritional outcomes: Evidence from Brazil

Recent studies reported that the age of primary school enrolment is a major driver of educational achievement and adult income, but its impacts on childhood health and nutrition remain largely unknown, particularly in developing countries where childhood stunting and overweight coexist. In Brazil, children are supposed to enrol in primary school the year they turn 6. Using a database of middle school students in Brazil based on a 2015 survey, I implemented an instrumental variables strategy using quasi-exogenous variations in the students’ birthdates to isolate the impact of late primary school enrolment (i.e., older than 6 when enrolled) on height-for-age and body mass-for-age indicators. Overall, late enrolment has protective effects against hazardous weight gain (−0.14 z-score unit) but significantly increases the risk of moderate stunting (by 1.5% points). Heterogeneity in family backgrounds may explain these results. Indeed, delayed school enrolment is particularly detrimental for the nutritional status of students from underprivileged settings. In terms of public policy, rather than changing school starting age, this study highlights the importance of focusing on pathways to fight both stunting and overweight conditions in Brazilian children.

Longitudinal physical performance and blood pressure changes in older women: Findings form the women's health initiative

BackgroundThis study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. Methods5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65–69 y; 70–79 y). ResultsOverall, each z-score unit increment in grip strength was associated with 0.59 mmHg (95% CI 0.10, 1.08) higher SBP, and 0.39 mmHg (95% CI 0.11, 0.67) higher DBP. In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.81; 95% CI 0.23–1.39), among antihypertensive medication users (0.93; 95% CI 0.44, 1.41) and non-users (0.37; 95% CI 0.03, 0.71), and in those aged 65–69 y (0.64; 95% CI 0.04, 1.24). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70–79 y. Associations between any performance measure and pulse pressure change were not significant. ConclusionThese results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age.

Mother's Own Milk and Its Relationship to Growth and Morbidity in a Population-based Cohort of Extremely Preterm Infants.

ABSTRACTObjectives:The aim of the study was to evaluate the relationships between intake of mother's own milk (MOM), compared with intake of pasteurized donor milk (DM), and postnatal growth, incidence of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD), in extremely preterm infants.Methods:Swedish population-based cohort of surviving extremely preterm infants born 2004 to 2007. Exposure to MOM and DM was investigated from birth until 32 weeks postmenstrual age (PMA) in 453 infants. Primary outcome variables were change in z-score (Δ) from birth to 32 weeks PMA for weight, length, and head circumference (HC). Secondary outcomes were incidence of ROP and BPD. Mixed models adjusting for confounders were used to investigate the association between exposures and outcomes.Results:Infants’ mean gestational age (GA) was 25.4 weeks. Unadjusted, MOM (per 10 mL · kg−1 · day−1) was associated with Δweight and ΔHC with beta estimates of 0.03 z-score units (95% CI, 0.02–0.04, P < 0.001) and 0.03 z-score units (95% CI, 0.01–0.05, P = 0.003), respectively. After adjustment for predefined confounders, the association remained significant for Δweight and ΔHC. A similar pattern was found between Δweight and each 10% increase of MOM. Unadjusted, a higher intake of MOM (mL · kg−1 · day−1) was significantly associated to a lower probability of any ROP and severe ROP; however, these associations did not remain in the adjusted analyses. No associations were found between MOM (mL · kg−1 · day−1) and BPD. Moreover, no associations were found between DM and growth or morbidity outcomes.Conclusions:An increased intake of MOM, as opposed to DM (and not formula feeding), was associated with improved postnatal weight gain and HC growth from birth until 32 weeks PMA in extremely preterm infants. Interventions aiming at increasing early intake of unpasteurized MOM for extremely preterm infants should be encouraged.

Maternal language disparities in neonatal intensive care unit outcomes.

To examine associations of maternal primary language with neonatal intensive care unit (NICU) outcomes (mother's milk at discharge, necrotizing enterocolitis [NEC], late-onset sepsis, weight gain) DESIGN: We performed a retrospective cohort study of mother-infant dyads (<34 weeks' gestation) in 9 NICUs (1/2016-12/2019), examining associations of maternal language (English [ref], Spanish, Other) with NICU outcomes, adjusting for birth weight for gestational age z-score, race/ethnicity, maternal age, and clustering by hospital. Among 1402 mothers, 85% spoke English, 7% spoke Spanish, and 7% spoke another language. Compared to English, infants with Spanish-speaking mothers had slower growth (-0.34 z-score units [-0.58, -0.10]). Infants with other non-English-speaking mothers had increased mother's milk at discharge (aOR 1.48 [1.18, 1.85]), NEC (aOR 1.43 [1.05, 1.95]), late-onset sepsis (aOR 2.84) [1.67, 4.83] and slower growth (-0.17 z-score units [-0.29, -0.05]). After adjustments, preterm infants with non-English-speaking mothers had worse outcomes than infants with English-speaking mothers.

Central Obesity, Cardiometabolic Risk, and Cognitive Change in the Study of Latinos - Investigation of Neurocognitive Aging.

The relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos. To understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos. Participants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol). Central obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =-0.165, p < 0.001) and to more pronounced cognitive declines over the average 7 years (ΔGlobalCognition = -0.109, p < 0.05); this was consistent across cognitive domains. Central obesity alone was not associated with cognitive function. However, presence of both central obesity and cardiometabolic abnormalities was robustly predictive of cognition and 7-year cognitive declines, suggesting that in combination these factors may alter the cognitive trajectories of middle-aged and older Hispanics/Latinos.

Examining the measurement equivalence of the Maslach Burnout Inventory across age, gender, and specialty groups in US physicians

BackgroundDisparities in US physician burnout rates across age, gender, and specialty groups as measured by the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI) are well documented. We evaluated whether disparities in US physician burnout are explained by differences in the MBI’s functioning across physician age, gender, and specialty groups.MethodsWe assessed the measurement equivalence of the MBI across age, gender, and specialty groups in multi-group item response theory- (IRT-) based differential item functioning (DIF) analyses using secondary, cross-sectional survey data from US physicians (n = 6577). We detected DIF using two IRT-based methods and assessed its impact by estimating the overall average difference in groups’ subscale scores attributable to DIF. We assessed DIF’s practical significance by comparing differences in individuals’ subscale scores and burnout prevalence estimates from models unadjusted and adjusted for DIF.ResultsWe detected statistically significant age-, gender-, and specialty- DIF in all but one MBI item. However, in all cases, average differences in expected subscale-level scores due to DIF were < 0.10 SD on each subscale. Differences in physicians’ individual-level subscale scores and burnout symptom prevalence estimates across DIF- adjusted and unadjusted IRT models were also small (in all cases, mean absolute differences in individual subscale scores were < 0.04 z-score units; prevalence estimates differed by < 0.70%).ConclusionsAge-, gender-, and specialty-related disparities in US physician burnout are not explained by differences in the MBI’s functioning across these demographic groups. Our findings support the use of the MBI as a valid tool to assess age-, gender-, and specialty-related disparities in US physician burnout.

Association of Childhood Lead Exposure With MRI Measurements of Structural Brain Integrity in Midlife

Childhood lead exposure has been linked to disrupted brain development, but long-term consequences for structural brain integrity are unknown. To test the hypothesis that childhood lead exposure is associated with magnetic resonance imaging (MRI) measurements of lower structural integrity of the brain in midlife. The Dunedin Study followed a population-representative 1972-1973 birth cohort in New Zealand (N = 564 analytic sample) to age 45 years (until April 2019). Childhood blood lead levels measured at age 11 years. Structural brain integrity at age 45 years assessed via MRI (primary outcomes): gray matter (cortical thickness, surface area, hippocampal volume), white matter (white matter hyperintensities, fractional anisotropy [theoretical range, 0 {diffusion is perfectly isotropic} to 100 {diffusion is perfectly anisotropic}]), and the Brain Age Gap Estimation (BrainAGE), a composite index of the gap between chronological age and a machine learning algorithm-estimated brain age (0 indicates a brain age equivalent to chronological age; positive and negative values represent an older and younger brain age, respectively). Cognitive function at age 45 years was assessed objectively via the Wechsler Adult Intelligence Scale IV (IQ range, 40-160, standardized to a mean of 100 [SD, 15]) and subjectively via informant and self-reports (z-score units; scale mean, 0 [SD, 1]). Of 1037 original participants, 997 were alive at age 45 years, of whom 564 (57%) had received lead testing at age 11 years (302 [54%] male) (median follow-up, 34 [interquartile range, 33.7-34.7] years). Mean blood lead level at age 11 years was 10.99 (SD, 4.63) μg/dL. After adjusting for covariates, each 5-μg/dL higher childhood blood lead level was significantly associated with 1.19-cm2 smaller cortical surface area (95% CI, -2.35 to -0.02 cm2; P = .05), 0.10-cm3 smaller hippocampal volume (95% CI, -0.17 to -0.03 cm3; P = .006), lower global fractional anisotropy (b = -0.12; 95% CI, -0.24 to -0.01; P = .04), and a BrainAGE index 0.77 years older (95% CI, 0.02-1.51 years; P = .05) at age 45 years. There were no statistically significant associations between blood lead level and log-transformed white matter hyperintensity volume (b = 0.05 log mm3; 95% CI, -0.02 to 0.13 log mm3; P = .17) or mean cortical thickness (b = -0.004 mm; 95% CI, -0.012 to 0.004 mm; P = .39). Each 5-μg/dL higher childhood blood lead level was significantly associated with a 2.07-point lower IQ score at age 45 years (95% CI, -3.39 to -0.74; P = .002) and a 0.12-point higher score on informant-rated cognitive problems (95% CI, 0.01-0.23; P = .03). There was no statistically significant association between childhood blood lead levels and self-reported cognitive problems (b = -0.02 points; 95% CI, -0.10 to 0.07; P = .68). In this longitudinal cohort study with a median 34-year follow-up, higher childhood blood lead level was associated with differences in some MRI measures of brain structure that suggested lower structural brain integrity in midlife. Because of the large number of statistical comparisons, some findings may represent type I error.

Sample size and sample composition for constructing growth reference centiles.

Growth reference centile charts are widely used in child health to assess weight, height and other age-varying measurements. The centiles are easy to construct from reference data, using the LMS method or GAMLSS (Generalised Additive Models for Location Scale and Shape). However, there is as yet no clear guidance on how to design such studies, and in particular how many reference data to collect, and this has led to study sizes varying widely. The paper aims to provide a theoretical framework for optimally designing growth reference studies based on cross-sectional data. Centiles for weight, height, body mass index and head circumference, in 6878 boys aged 0–21 years from the Fourth Dutch Growth Study, were fitted using GAMLSS. The effect on precision of varying the sample size and the distribution of measurement ages (sample composition) was explored by fitting a series of GAMLSS models to simulated data. Sample composition was defined as uniform on the ageλ scale, where λ was chosen to give constant precision across the age range. Precision was measured on the z-score scale, and was the same for all four measurements, with a standard error of 0.041 z-score units for the median and 0.066 for the 2nd and 98th centiles. Compared to a naïve calculation, the process of smoothing the centiles increased the notional sample size two- to threefold by ‘borrowing strength’. The sample composition for estimating the median curve was optimal for λ=0.4, reflecting considerable over-sampling of infants compared to children. However, for the 2nd and 98th centiles, λ=0.75 was optimal, with less infant over-sampling. The conclusion is that both sample size and sample composition need to be optimised. The paper provides practical advice on design, and concludes that optimally designed studies need 7000–25,000 subjects per sex.

Human milk composition differs by maternal BMI in the first 9 months postpartum

Studies indicate that maternal weight status modulates human milk composition; however, results are conflicting. Our objective was to examine the relation between maternal body composition and human milk macronutrients and bioactive components and also their association with infant daily intakes and body composition. Human milk samples were obtained from a longitudinal study (NCT01131117) in normal weight (NW: 18.5-24.9 kg/m2, n=88) and overweight/obese (OW: 25-35 kg/m2, n=86) women between 0.5 and 9 mo postpartum. Macronutrient content was estimated using mid-infrared spectroscopy. Leptin, insulin, and C-reactive protein (CRP) were measured using electrochemiluminescence immunoassays. Infant body composition was obtained using quantitative MRI. Linear mixed models were adjusted for postpartum age and infant sex. Human milk in OW mothers was higher in fat and protein and lower in carbohydrate content at some time points compared with that in NW mothers. Human milk leptin, insulin, and CRP concentrations were higher in OW mothers compared with NW mothers, with infants of OW mothers exposed to 1.5-2.5 times higher concentrations of leptin and insulin compared with infants of NW mothers. Similar results were observed when concentrations were normalized to infant daily intake and body weight. The effect sizes of infant daily intakes associated with infant growth parameters were small for macronutrients [0.005-0.05 z-score units and 0.02-0.45 fat mass index (FMI) or fat-free mass index units per unit of change in composition, P<0.05]. Larger effect sizes were seen with human milk insulin and leptin (0.24 z-score units and 0.37-1.15 FMI units per unit of change in composition, P<0.05). These findings demonstrate that infants of OW mothers are exposed to higher concentrations of insulin, leptin, and, to a lesser extent, CRP. The bioavailability of these 3 human milk bioactives and their mechanisms of action in the infant are unclear.This trial was registered at clinicaltrials.gov as NCT01131117.

Age of cow milk introduction and growth among 3-5-year-old children.

To evaluate the association between the age of cow milk introduction and childhood growth. A secondary analysis of a prospective cohort study. Toronto, Canada. Healthy children <5 years of age enrolled in the TARGet Kids! practice-based research network. The primary exposure was the age of cow milk introduction. The primary outcome was height-for-age z-score. Secondary outcomes were volume of cow milk consumed (cups/d) and BMI z-score. Outcomes were measured at the last visit before 5 years of age. Multiple linear regression was used to examine these relationships. Among 1981 children, introduction of cow milk at a younger age was associated with greater height by 3-5 years of age (P < 0·001). Each month earlier that cow milk was introduced was associated with 0·03 higher height-for-age z-score unit (95 % CI -0·05, -0·02) or 0·1 cm (95 % CI -0·15, -0·12 cm). At 4 years of age, the height difference between a child introduced to cow milk at 9 v. 12 months was 0·4 cm (95 % CI -0·45, -0·35cm). There was no association between the timing of cow milk introduction and volume of cow milk consumed per day or BMI z-score. Earlier introduction of cow milk was associated with greater height but not with weight status in children aged 3-5 years. Further research is needed to understand the casual relationship between earlier cow milk consumption and childhood height. These findings may be important for paediatricians and parents when considering when to introduce cow milk.

36-LB: Linoleic Acid Derived Oxylipins, Memory, and Microvascular Retinal Complications in Patients with Type 2 Diabetes Mellitus

Introduction: Memory decline is accelerated in type 2 diabetes mellitus (T2DM), and it is thought that microvascular disease may be a contributor. Oxylipins, bioactive lipid species derived from polyunsaturated free fatty acids such as linoleic acid, can act on small vessels. Cytochrome p450 derived epoxides may be immunologically active, whereas their hydrolysis into diols by soluble epoxide hydrolase (sEH) may render them inactive or cytotoxic. We examine linoleic acid epoxide and diol concentrations in peripheral blood and their associations with memory performance and retinal microvascular disease in patients with T2DM or prediabetes. Methods: Patients with T2DM or prediabetes were recruited from 3 sites. Memory was assessed via California Verbal Learning Test 2nd Edition (CVLT-II). Patient history of retinopathy was recorded. Serum oxylipin concentrations were measured via ultra-high-performance liquid chromatography tandem mass-spectrometry. Results: In people with T2DM or prediabetes (n=76, 55% women, 63±9 years old, HbA1C=7.4±1.2% mmol/mol, duration of diabetes 8±10 years), 9.2% had retinopathy, and the mean CVLT-II was -0.07±1.01 Z-score units (indicating generally average performance). The linoleic acid derived epoxide 12(13)-epoxyoctadecenoic acid concentration was negatively correlated with CVLT-II performance (β=-0.298, p=0.003), whereas the diol derived from that species (12,13-dihydroxyoctadecenoic acid) was elevated in people with retinopathy (9.1±4.1 nM vs. 6.5±11.5 nM, U=72.0, p=0.008). Discussion: Oxylipins generated by cytochrome p450 and sEH should be explored as potential biomarkers for cognitive complications and microvascular disease in T2DM. The observed relationships might suggest the presence of a cytochrome p450-mediated response that may generate differential response and lack benefit in T2DM, possibly due to sEH-mediated conversion of epoxides into diols, warranting further study. Disclosure S.K. Wong: None. M.M. Nguyen: None. C. Major-Orfao: None. K.L. Lanctôt: None. N. Herrmann: None. P. Oh: None. B.R. Shah: None. J. Gilbert: Speaker’s Bureau; Self; Abbott, Amgen, Ascensia Diabetes Care. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. A. Assal: None. I. Halperin: Advisory Panel; Self; Tandem Diabetes Care. Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Novo Nordisk Inc., Sanofi. P. Yang: None. T. Pedersen: None. A. Taha: None. W. Swardfager: None. Funding Canadian Institutes of Health Research (410010992)

Human Milk Composition Differs by Maternal BMI in the First 9 Months Postpartum

Abstract Objectives Recent studies indicate that human milk composition is modulated by maternal weight status; however, results are conflicting. The objective of this study was to examine the relationship between maternal body composition and human milk macronutrients and bioactive components, as well as the association between infant daily intakes and infant body composition. Methods Human milk samples (N = 990) were obtained from a longitudinal study (NCT#0,113,1117) in normal weight (NW: 18.5–24.9 kg/m,2 N = 88) and overweight/obese (OW: 25–35 kg/m,2 N = 86) women between 0.5 and 9 months postpartum. Macronutrient content was estimated using mid-infrared spectroscopy (MIRIS AB). Leptin, insulin, C-reactive protein (CRP), IL-6, IL-8 and TNF-α were measured using electrochemiluminescence immunoassays (Meso Scale Diagnostics). Infant body composition was obtained using quantitative magnetic resonance (Echo-MRI-AH). Linear mixed models adjusted for postpartum age and infant sex. Results Human milk was higher in fat and protein, and lower in carbohydrate content at only a few time points in OW compared to NW mothers. Human milk leptin and insulin concentrations were higher in OW mothers throughout lactation and CRP content differed at most time points compared to NW mothers. Similar results were observed when concentrations were normalized to infant daily intake and body weight. The effect sizes of infant daily intakes associated with infant growth parameters were small for macronutrients (0.005 to 0.05 Z-score units and 0.02 to 0.45 fat mass index (FMI)/fat free mass index (FFMI) units per unit of change in composition). Larger effect sizes were seen with human milk insulin and leptin, with infants of OW mothers exposed to 1.5 to 2.5 times higher concentrations compared to infants of NW mothers. Conclusions This study allows for a more comprehensive understanding of maternal BMI effects on human milk composition and its association with infant growth. Of note, the concentrations of leptin and insulin in human milk from OW mothers were higher than those in milk from NW mothers, resulting in higher daily intakes by their infants and modulation of FMI from 0.5 to 9 months postpartum. This study demonstrates the value of considering both human milk composition and infant daily intake when assessing infant growth. Funding Sources USDA/ARS Project # 6026–51,000-012–06S, NIH R01 DK107516.

Long-Term Risk Factors for Dilatation of the Proximal Aorta in a Large Cohort of Children With Bicuspid Aortic Valve.

Patients with bicuspid aortic valve (BAV) have a higher risk of developing aortic valve dysfunction and progressive proximal aorta dilatation, which can lead to aortic dissection. To this day, identification of children at risk of developing severe aortic dilatation during their pediatric follow-up is still challenging because most studies were restricted to adult subjects. The overarching goal of this study was to identify risk factors of aortic dilatation in children with BAV. We extracted clinical and echocardiographic data of all BAV subjects aged 0 to 20 years followed at Centre Hospitalier Universitaire Sainte-Justine between 1999 and 2016. We excluded subjects with concomitant heart defects and conditions affecting proximal aorta dimensions. Proximal aorta diameters (expressed as Z scores) were modeled in relation to age and potential predictive variables in a linear mixed model. The primary outcome was the rate of dilatation. We included 761 subjects (3134 echocardiograms) in final analyses. The mean ascending aorta Z score progression rate for BAV patient with a normally functioning aortic valve was estimated at 0.05 Z score unit per year. The strongest predictors of an increased dilatation rate were severe aortic stenosis, moderate and severe aortic regurgitation, and uncorrected coarctation of the aorta. Aortic valve leaflet fusion pattern and sex were not associated with progression rate. Children with a normally functioning BAV exhibited a very slow proximal aorta dilatation rate. Ascending aorta dilatation rate was significantly increased in patients with more than mild aortic valve dysfunction but was independent from BAV leaflet fusion type.