ABSTRACT
OBJECTIVE: To translate data relating childhood cardiovascular (CV) risk factors and adult CV disease and type 2 diabetes mellitus (T2DM) to clinically actionable values. STUDY DESIGN: A prospective observational study (n=38,589) in the International Childhood Cardiovascular Cohort (i3C) Consortium. Children at age 3 through 19 years were enrolled in the 1970s and 1980s and followed for over 30 years. Five childhood CV risk factors (smoking, body mass index [BMI], systolic blood pressure [SBP], triglycerides [TG], and total cholesterol [TC]) were related to adult CV events. Secondary analyses in a subset included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose and insulin level. Age- and sex-specific z-scores were calculated for each risk factor, and a combined-risk z-score was calculated by averaging z-scores for the 5 key CV risk factors. Risk factor z-scores were back-transformed to natural units for clinical interpretation, with hazard ratios for adult CV events presented in color coded tables (green: no increased risk; orange: 1.4 to <2.0-fold increased risk; red: at least doubling of risk). Risk levels for development of adult T2DM based on BMI, glucose, and insulin were similarly calculated and presented. RESULTS: Increased risk for CV events was observed at levels lower than currently defined abnormal clinical thresholds except for TC. Doubling of risk was observed at high normal levels just below the clinical cut point for abnormality. Risk for adult T2DM began at levels of BMI and glucose currently considered normal. CONCLUSION: Based on data showing significant relationships between childhood CV risk factors and adult CV events and T2DM, this study shows that risk in childhood begins below levels currently considered normal.
ABSTRACT
Importance: Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels. Objective: To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach. Design, Setting, and Participants: This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023. Main Outcomes and Measures: The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs. Results: A total of 10â¯634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period. Conclusions and Relevance: In this cohort study of 10â¯634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.
Subject(s)
Cardiovascular Diseases , Heart Disease Risk Factors , Humans , Male , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Female , Child , Prospective Studies , Finland/epidemiology , Middle Aged , Adolescent , Adult , Body Mass Index , Australia/epidemiology , Smoking/epidemiology , Smoking/adverse effects , Risk Factors , United States/epidemiology , Blood Pressure , IncidenceABSTRACT
BACKGROUND: Accumulating evidence shows that peri-conceptional and in-utero exposures have lifetime health impacts for mothers and their offspring. OBJECTIVES: We conducted a Follow-Up Study of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial with two objectives. First, we determined if women who enrolled at the Utah site (N = 1001) of the EAGeR trial (2007-2011, N = 1228) could successfully be contacted and agree to complete an online questionnaire on their reproductive, cardio-metabolic, and offspring respiratory health 9-14 years after original enrollment. Second, we evaluated if maternal exposure to low-dose aspirin (LDA) during pregnancy was associated with maternal cardio-metabolic health and offspring respiratory health. METHODS: The original EAGeR study population included women, 18-40 years of age, who had 1-2 prior pregnancy losses, and who were trying to become pregnant. At follow-up (2020-2021), participants from the Utah cohort completed a 13-item online questionnaire on reproductive and cardio-metabolic health, and those who had a live birth during EAGeR additionally completed a 7-item questionnaire on the index child's respiratory health. Primary maternal outcomes included hypertension and hypercholesterolemia; primary offspring outcomes included wheezing and asthma. RESULTS: Sixty-eight percent (n = 678) of participants enrolled in the follow-up study, with 10% and 15% reporting maternal hypertension and hypercholesterolemia, respectively; and 18% and 10% reporting offspring wheezing and asthma. We found no association between maternal LDA exposure and hypertension (risk difference [RD] -0.001, 95% confidence interval [CI] -0.05, 0.04) or hypercholesterolemia (RD -0.01, 95% CI -0.06, 0.05) at 9-14 years follow-up. Maternal LDA exposure was not associated with offspring wheezing (RD -0.002, 95% CI -0.08, 0.08) or asthma (RD 0.13, 95% CI 0.11, 0.37) at follow-up. Findings remained robust after considering potential confounding and selection bias. CONCLUSIONS: We observed no association between LDA exposure during pregnancy and maternal cardiometabolic or offspring respiratory health.
ABSTRACT
BACKGROUND & AIMS: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children. METHODS: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15. RESULTS: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74. CONCLUSIONS: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.
ABSTRACT
INTRODUCTION: Three widely referenced growth curves classify infant birth anthropometric measurements as small (SGA), appropriate (AGA), or large (LGA) for gestational age (GA) differently. We assessed how these differences in assignment affect the identification and prediction of neonatal intensive care unit (NICU) mortality risk in US preterm infants. METHODS: Birth data of infants admitted to NICUs from the Pediatrix Clinical Data Warehouse (2013-2018) were analyzed. Birth weight, length, and head circumference of 46,724 singleton infants (24-32 weeks GA) were classified as SGA, AGA, or LGA using the Olsen, Fenton, and INTERGROWTH-21st curves. NICU mortality risk based on birth size classification was analyzed using unadjusted and adjusted logistic regression stratified by GA. RESULTS: Odds of mortality were increased with SGA classification at all GAs, size measurements, and curve sets, compared with AGA infants. LGA classification for weight was associated with lower mortality risk at 24 weeks GA and higher risk at 30 weeks GA. Odds of mortality did not differ significantly across curve sets. Classification of size at birth alone had relatively low predictive ability to identify mortality risk, with unadjusted AUCs near 0.5 for all analyses. CONCLUSION: There were no significant differences across curve sets in predicting mortality. Classification of size at birth is a relatively imprecise method to identify infants at risk for NICU mortality.
Subject(s)
Birth Weight , Gestational Age , Infant Mortality , Infant, Small for Gestational Age , Intensive Care Units, Neonatal , Humans , Infant, Newborn , Female , Male , United States/epidemiology , Growth Charts , Infant , Infant, Premature/growth & development , Logistic Models , Risk Assessment , Risk FactorsABSTRACT
Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.
Subject(s)
Cardiovascular Diseases , Cholesterol, LDL , Dyslipidemias , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Cholesterol/blood , Cholesterol, LDL/blood , Dyslipidemias/epidemiology , Dyslipidemias/blood , Finland/epidemiology , Heart Disease Risk Factors , Incidence , Prospective Studies , United States/epidemiologyABSTRACT
Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is common and can be seen as early as in utero. A growing body of literature suggests that gestational and early life exposures modify the risk of MASLD development in children. These include maternal risk factors, such as poor cardiometabolic health (e.g., obesity, gestational diabetes, rapid weight gain during pregnancy, and MASLD), as well as periconceptional dietary exposures, degree of physical activity, intestinal microbiome, and smoking. Paternal factors, such as diet and obesity, also appear to play a role. Beyond gestation, early life dietary exposures, as well as the rate of infant weight gain, may further modify the risk of future MASLD development. The mechanisms linking parental health and environmental exposures to pediatric MASLD are complex and not entirely understood. In conclusion, investigating gestational and developmental contributors to MASLD is critical and may identify future interventional targets for disease prevention.
Subject(s)
Fatty Liver , Obesity , Infant , Female , Pregnancy , Child , Humans , Environmental Exposure , Exercise , Weight GainABSTRACT
A qualitative, community-engaged assessment was conducted to identify needs and priorities for infant obesity prevention programs among mothers participating in home visiting programs. Thirty-two stakeholders (i.e., community partners, mothers, home visitors) affiliated with a home visiting program serving low-income families during the prenatal to age three period participated in group level assessment sessions or individual qualitative interviews. Results indicated families face many challenges to obesity prevention particularly in terms of healthy eating. An obesity prevention program can address these challenges by offering realistic feeding options and non-judgmental peer support, improving access to resources, and tailoring program content to individual family needs and preferences. Informational needs, family factors in healthy eating outcomes, and the importance of access and awareness of programs were also noted. To ensure the cultural- and contextual-relevance of infant obesity prevention programs for underserved populations, needs and preferences among community stakeholders and the focal population should be used as a roadmap for intervention development.
Subject(s)
Pediatric Obesity , Infant , Female , Pregnancy , Humans , Pediatric Obesity/prevention & control , Needs Assessment , Mothers , Poverty , CounselingABSTRACT
BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Male , Adult , Female , Child , Humans , Cholesterol, LDL , Prospective Studies , Cholesterol , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Lipoproteins , Risk Factors , Cholesterol, HDLABSTRACT
Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate "human-like" obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more "human-like" approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.
Subject(s)
Metabolic Diseases , Obesity, Maternal , Prenatal Exposure Delayed Effects , Humans , Female , Male , Mice , Pregnancy , Animals , Cohort Studies , Housing , Diet, High-Fat/adverse effects , Mice, Inbred C57BL , Obesity/etiology , Obesity/metabolism , Metabolic Diseases/etiologyABSTRACT
OBJECTIVES: To use growth data from electronic health records to describe and model infant growth (weight velocity and peak body mass index [pBMI]) characteristics. STUDY DESIGN: We extracted data from all children born at ≥34 weeks of gestation within one health system between 2014 and 2017. After excluding implausible growth data with an algorithm created for childhood growth, we estimated pBMI, peak weight and length velocities, and the odds of obesity at 2 years, adjusted for race, sex, ethnicity, and birth weight, by the magnitude of peak weight velocity, peak length velocity, and pBMI. RESULTS: Among 6425 children (41% White, 28% Black, 26% other race; 16% Hispanic ethnicity), mean pBMI was 17.9 kg/m2 (SD 1.5) and mean age at pBMI was 9.6 months (SD 2.7). Mean peak weight velocity was 949 g (SD 165) per 2 weeks, and the mean peak length velocity was 3.4 cm (SD 0.3) per 2 weeks. Children with obesity at 2 years (n = 931, 14.5%) were more likely to be Hispanic, had greater peak weight and peak length velocities, and had 2 kg/m2 greater magnitude of pBMI than children without obesity. For each unit increase in pBMI, children had more than 4 times greater odds of obesity at age 2 years. CONCLUSIONS: In a large sample of infants with clinical growth data tracked via electronic health records, we found associations between the magnitude and timing of peak infant BMI and obesity at 2 years of age.
Subject(s)
Electronic Health Records , Obesity , Child , Infant , Humans , Child, Preschool , Body Mass Index , Retrospective Studies , Birth WeightABSTRACT
BACKGROUND: Lipoprotein subfraction concentrations have been shown to change as gestation progresses in resource-rich settings. The objective of the current study was to evaluate the impact of pregnancy on different-sized lipoprotein particle concentrations and compositions in a resource-poor setting. METHOD: Samples were collected from pregnant women in rural Gambia at enrollment (8-20 weeks), 20 weeks, and 30 weeks of gestation. Concentrations of different-sized high-density, low-density, and triglyceride-rich lipoprotein particles (HDL, LDL, and TRL, respectively) were measured by nuclear magnetic resonance in 126 pooled plasma samples from a subset of women. HDL was isolated and the HDL proteome evaluated using mass spectroscopy. Subfraction concentrations from women in The Gambia were also compared to concentrations in women in the U.S. in mid gestation. RESULTS: Total lipoprotein particles and all-sized TRL, LDL, and HDL particle concentrations increased during gestation, with the exception of medium-sized LDL and HDL particles which decreased. Subfraction concentrations were not associated with infant birth weights, though relationships were found between some lipoprotein subfraction concentrations in women with normal versus low birth weight infants (< 2500 kg). HDL's proteome also changed during gestation, showing enrichment in proteins associated with metal ion binding, hemostasis, lipid metabolism, protease inhibitors, proteolysis, and complement activation. Compared to women in the U.S., Gambian women had lower large- and small-sized LDL and HDL concentrations, but similar medium-sized LDL and HDL concentrations. CONCLUSIONS: Most lipoprotein subfraction concentrations increase throughout pregnancy in Gambian women and are lower in Gambian vs U.S. women, the exception being medium-sized LDL and HDL particle concentrations which decrease during gestation and are similar in both cohorts of women. The proteomes of HDL also change in ways to support gestation. These changes warrant further study to determine how a lack of change or different changes could impact negative pregnancy outcomes.
Subject(s)
Lipoproteins , Proteome , Humans , Female , Infant , Pregnancy , Gambia , Triglycerides , Birth Weight , Lipoproteins, LDLABSTRACT
BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.
Subject(s)
Atherosclerosis , Cardiovascular Diseases , Adult , Child , Humans , Adolescent , Lipoprotein(a) , Carotid Intima-Media Thickness , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Risk Assessment , Risk Factors , Atherosclerosis/epidemiology , Atherosclerosis/diagnosis , Cholesterol, LDLABSTRACT
BACKGROUND AND OBJECTIVES: Changes in BMI z score (BMIz) are widely used in weight control programs and interventions to monitor changes in body fatness, but this metric may not be optimal. We examined the ability of 3 BMI metrics to assess adiposity change among children with a wide range of BMIs. METHODS: The sample comprised 343 3-year-old children with serial measurements of BMI and body fatness every 4 months over 4 years. We compared correlations between changes in body fatness, calculated with dual-energy-x-ray absorptiometry, and changes in 3 BMI metrics: BMIz and percentage of the 50th (%50th) and 95th (%95th) percentiles in the CDC growth charts. RESULTS: About 21% of the participants were Black and 79% were white. Changes in body fatness over 4 years were more strongly associated with changes in %50th and %95th than with changes in BMIz. Correlations with %body fat among all children were r = 0.64 for BMIz versus r = 0.77 to 0.78 for %50th and %95th (P < .001 for differences between the correlations). Stratified analyses showed the difference between the correlations were similar among boys and girls, among white children and Black children, and among children without obesity and those with obesity. CONCLUSIONS: Changes in adiposity among young children are better captured by expressing changes in BMI as a percentage of the 50th or 95th percentiles instead of BMIz change. Using the best BMI metric will allow pediatricians to better assess a child's change in body fatness over time.
Subject(s)
Adiposity , Obesity , Male , Female , Humans , Child, Preschool , Body Mass Index , Obesity/diagnosis , Adipose Tissue , BenchmarkingABSTRACT
Background: Understanding lifecourse trajectories of body-mass index (BMI) is important for identifying groups at high risk of poor health and potential target points for intervention. This study aimed to describe BMI trajectories from childhood to mid-adulthood in four population-based cohorts established in the 1970s and 1980s and to identify childhood sociodemographic factors related to trajectory membership. Methods: Between Dec 17, 1970 and Dec 15, 1994, data were collected at the first visit from 9830 participants from the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes participants from Australia (1985), Finland (1980) and the USA (1970-1994). Participants had at least three measures of height and weight, including one in childhood (6-18 years) and one in adulthood (>18 years), and were aged 30-49 years at last measurement. Latent Class Growth Mixture Modelling was used to identify lifecourse BMI trajectory groups and log multinomial regression models were fit to identify their childhood sociodemographic predictors. Findings: Five consistent BMI trajectory groups were identified amongst the four cohorts: persistently low (35.9-58.6%), improving from high (0.7-4.8%), progressing to moderate (9.3-43.7%), progressing to high (1.1-6.0%), and progressing to very high (0.7-1.3%). An additional three BMI trajectory groups were identified in some, but not all, cohorts: adult onset high (three cohorts; 1.8-20.7%), progressing to moderate-high (two cohorts; 5.2-13.8%), and relapsing yo-yoers (alternating upward and downward; one cohort; 1.3%). In pooled analyses, each predictor variable in childhood, including age, gender, parental education and race, was associated with increased likelihood of belonging to the most (e.g., improving from high) and least (e.g., progressing to very high) favourable BMI trajectory groups, suggesting a U-shaped (or inverse U-shaped) pattern of association. Interpretation: Five consistent BMI trajectory groups were identified across four cohorts from Australia, Finland, and the USA, mainly across two eras of birth. While most participants remained on a persistently low trajectory (50%), many demonstrated worsening BMI trajectories (47%), with only few demonstrating improving trajectories (<5%). Age, gender, parental education, and race appear to be important predictors of BMI trajectory group membership and need consideration in preventive and management strategies. Funding: This study was supported by funding from the National Institutes of Health, National Heart, Lung and Blood Institute (grant number R01 HL121230).
ABSTRACT
BACKGROUND: Parental feeding styles, including the emotional environment parents create to modify a child's eating behaviors, have been associated with measures of adiposity in cross-sectional studies. The longitudinal relation between parental feeding styles in early infancy and adiposity in later infancy/toddlerhood are scant and have shown mixed results, particularly in families from low-income households. OBJECTIVES: This study examined the relation between parental feeding styles and infant BMI z-score trajectories between 6 and 18 mo in families from low-income households. METHODS: Parent-infant dyads were recruited during the infant's 6-, 9-, or 12-mo well-child visit. Feeding styles were assessed using the Infant Feeding Style Questionnaire (IFSQ). Infant anthropometrics from birth through 18 mo were extracted from the electronic medical record. BMI z-score slopes were estimated for each infant between 0-6 mo and 6-18 mo. Associations between feeding styles and BMI z-score slopes were examined using mixed models controlling for demographic, clinical, and feeding covariates. RESULTS: The final analytic sample included 198 dyads (69% Black; median infant age: 9.0 mo; IQR: 6.8-10.3 mo). The predominant parent feeding styles included the following: laissez-faire (30%), restrictive (28%), responsive (23%), and pressuring (19%). In adjusted models, the predominant feeding style at enrollment was associated with the BMI z-score slope between 6 and 18 mo, with the responsive feeding style exhibiting a steeper increase in BMI z-score than other feeding styles. Infant feeding style was not associated with BMI z-score slope between birth and 6 mo of age. Infants of parents who exhibited restrictive feeding styles were more likely to have a BMI ≥85th percentile at their last measurement. CONCLUSIONS: The predominant parent feeding style during infancy in a low-income population was associated with infant BMI z-score between 6 and 18 mo of age, but not earlier. Further studies are needed to better understand how predictive factors collectively contribute to BMI increase in the first 2 y.
Subject(s)
Parenting , Poverty , Body Mass Index , Child , Cross-Sectional Studies , Feeding Behavior/psychology , Humans , Infant , Obesity , Parenting/psychology , Parents/psychology , Surveys and QuestionnairesABSTRACT
BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear. METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohort (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression. RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events. CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).
Subject(s)
Cardiovascular Diseases , Adolescent , Adult , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Child, Preschool , Cholesterol , Female , Heart Disease Risk Factors , Humans , Male , Prospective Studies , Risk Factors , Young AdultABSTRACT
Accumulating evidence indicates that obesity and cardiometabolic risks become established early in life due to developmental programming and infants born as large for gestational age (LGA) are particularly at risk. This review summarizes the recent literature connecting LGA infants and early childhood obesity and cardiometabolic risk and explores potential preventive interventions in early infancy. With the rising obesity rates in women of childbearing age, the LGA birth rate is about 10%. Recent literature continues to support the higher rates of obesity in LGA infants. However, there is a knowledge gap for their lifetime risk for adverse cardiometabolic outcomes. Potential factors that may modify the risk in early infancy include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. The early postnatal period may be a critical window of opportunity for active interventions to mitigate or prevent obesity and potential adverse metabolic consequences in later life. A variety of promising candidate biomarkers for the early identification of metabolic alterations in LGA infants is also discussed. IMPACT: LGA infants are the greatest risk category for future obesity, especially if they experience rapid postnatal growth during infancy. Potential risk modifying secondary prevention strategies in early infancy in LGA infants include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. LGA infants may be potential low-hanging fruit targets for early preventive interventions in the fight against childhood obesity.
Subject(s)
Cardiovascular Diseases , Pediatric Obesity , Birth Weight , Body Mass Index , Cardiovascular Diseases/prevention & control , Child , Child, Preschool , Female , Gestational Age , Humans , Infant , Pediatric Obesity/prevention & control , Risk Factors , Weight GainABSTRACT
BACKGROUND: In high-income countries, cancer is the leading cause of death among middle-aged adults. Prospective data on the effects of childhood risk exposures on subsequent cancer mortality are scarce. METHODS: We examined whether childhood body mass index (BMI), blood pressure, glucose and lipid levels were associated with adult cancer mortality, using data from 21,012 children enrolled aged 3-19 years in seven prospective cohort studies from the U.S., Australia, and Finland that have followed participants from childhood into adulthood. Cancer mortality (cancer as a primary or secondary cause of death) was captured using registries. RESULTS: 354 cancer deaths occurred over the follow-up. In age-, sex, and cohort-adjusted analyses, childhood BMI (Hazard ratio [HR], 1.13; 95% confidence interval [CI] 1.03-1.24 per 1-SD increase) and childhood glucose (HR 1.22; 95%CI 1.01-1.47 per 1-SD increase), were associated with subsequent cancer mortality. In a multivariable analysis adjusted for age, sex, cohort, and childhood measures of fasting glucose, total cholesterol, triglycerides, and systolic blood pressure, childhood BMI remained as an independent predictor of subsequent cancer mortality (HR, 1.24; 95%CI, 1.03-1.49). The association of childhood BMI and subsequent cancer mortality persisted after adjustment for adulthood BMI (HR for childhood BMI, 1.35; 95%CI 1.12-1.63). CONCLUSIONS: Higher childhood BMI was independently associated with increased overall cancer mortality.