A Clinical Tool to Relate Youth Risk Factors to Adult Cardiovascular Events and Type 2 Diabetes: The International Childhood Cardiovascular Cohort Consortium.

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: This was a prospective observational study (n = 38 589) in the International Childhood Cardiovascular Cohort Consortium. Children at age 3 through 19 years were enrolled in the 1970s and 1980s and followed for more than 30 years. Five childhood CV risk factors (smoking, body mass index [BMI], systolic blood pressure, triglycerides, and total cholesterol) were related to adult CV events. Secondary analyses in a subset included low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, 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 on the basis of 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. CONCLUSIONS: On the basis of 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.

Cardiovascular Risk Factors in Childhood and Adulthood and Cardiovascular Disease in Middle Age.

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 10 634 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 10 634 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.

Gestational and Developmental Contributors of Pediatric MASLD.

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.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

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.

Childhood Cardiovascular Risk Factors and Adult Cardiovascular Events.

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.).

Obesity during childhood is associated with higher cancer mortality rate during adulthood: the i3C Consortium.

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.

Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?

OBJECTIVES: To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury. METHODS: Pre-pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study. RESULTS: Measures were strongly correlated at pre- and during-pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre-pregnancy and during-pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits. CONCLUSIONS: Pre- and during-pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.

Caregiver Influences on Eating Behaviors in Young Children: A Scientific Statement From the American Heart Association.

A substantial body of research suggests that efforts to prevent pediatric obesity may benefit from targeting not just what a child eats, but how they eat. Specifically, child obesity prevention should include a component that addresses reasons why children have differing abilities to start and stop eating in response to internal cues of hunger and satiety, a construct known as eating self-regulation. This review summarizes current knowledge regarding how caregivers can be an important influence on children's eating self-regulation during early childhood. First, we discuss the evidence supporting an association between caregiver feeding and child eating self-regulation. Second, we discuss what implications the current evidence has for actions caregivers may be able to take to support children's eating self-regulation. Finally, we consider the broader social, economic, and cultural context around the feeding environment relationship and how this intersects with the implementation of any actions. As far as we are aware, this is the first American Heart Association (AHA) scientific statement to focus on a psychobehavioral approach to reducing obesity risk in young children. It is anticipated that the timely information provided in this review can be used not only by caregivers within the immediate and extended family but also by a broad range of community-based care providers.

Childhood/Adolescent Smoking and Adult Smoking and Cessation: The International Childhood Cardiovascular Cohort (i3C) Consortium.

Background Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, <0.001). Similar patterns were observed for prediction of smoking during age forties. Among the 2465 smokers in their twenties, cessation by their forties was generally inverse to degree of smoking in ages 6 to 19 (P trend, <0.001). Prevalence of smoking during adolescence and adulthood was similar among US, Finnish, and Australian participants. Conclusions These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes.

The Preconception Period analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: Preconception health may have intergenerational influences. We have formed the PrePARED (Preconception Period Analysis of Risks and Exposures influencing health and Development) research consortium to address methodological, conceptual, and generalisability gaps in the literature. OBJECTIVES: The consortium will investigate the effects of preconception exposures on four sets of outcomes: (1) fertility and miscarriage; (2) pregnancy-related conditions; (3) perinatal and child health; and (4) adult health outcomes. POPULATION: A study is eligible if it has data measured for at least one preconception time point, has a minimum of selected core data, and is open to collaboration and data harmonisation. DESIGN: The included studies are a mix of studies following women or couples intending to conceive, general-health cohorts that cover the reproductive years, and pregnancy/child cohort studies that have been linked with preconception data. The majority of the participating studies are prospective cohorts, but a few are clinical trials or record linkages. METHODS: Data analysis will begin with harmonisation of data collected across cohorts. Initial areas of interest include nutrition and obesity; tobacco, marijuana, and other substance use; and cardiovascular risk factors. PRELIMINARY RESULTS: Twenty-three cohorts with data on almost 200 000 women have combined to form this consortium, begun in 2018. Twelve studies are of women or couples actively planning pregnancy, and six are general-population cohorts that cover the reproductive years; the remainder have some other design. The primary focus for four was cardiovascular health, eight was fertility, one was environmental exposures, three was child health, and the remainder general women's health. Among other cohorts assessed for inclusion, the most common reason for ineligibility was lack of prospectively collected preconception data. CONCLUSIONS: The consortium will serve as a resource for research in many subject areas related to preconception health, with implications for science, practice, and policy.

Prevalence of abnormal glucose metabolism in pediatric acute, acute recurrent and chronic pancreatitis.

Type 3C Diabetes, or diseases of the exocrine pancreas has been reported to occur in approximately 30% of adult patient with pancreatitis. The incidence of glucose abnormalities or risk factors that may predict the development of abnormal glucose in the pediatric pancreatitis population is not known. We performed a retrospective chart review from 1998-2016 for patients who carry the diagnosis of acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP). We extracted glucose values, HbA1c%, and data from oral glucose tolerance and mixed meal testing with timing in relation to pancreatic exacerbations. Patient characteristic data such as age, gender, body proportions, family history of pancreatitis, exocrine function and genetic mutations were also assessed. Abnormal glucose was based on definitions put forth by the American Diabetes Society for pre-diabetes and diabetes. Fifty-two patients had AP and met criteria. Of those, 15 (29%) had glucose testing on or after the first attack, 21 (40%) were tested on or after the second attack (in ARP patients) and 16 (31%) were tested after a diagnosis of CP. Of the patients tested for glucose abnormalities, 25% (13/52) had abnormal glucose testing (testing indicating pre-DM or DM as defined by ADA guidelines. A significantly higher proportion of the abnormal glucose testing was seen in patients (85%, 11/13) with a BMI at or greater than the 85th percentile compared to the normal glucose patients (28%, 11/39) (p = 0.0007). A significantly higher proportion of the abnormal glucose patients (77%, 10/13) had SAP during the prior AP episode to testing compared to the 10% (4/39) of the normal glucose patients (p<0.0001). Older age at DM testing was associated with a higher prevalence of abnormal glucose testing (p = 0.04). In our patient population, a higher proportion of glucose abnormalities were after the second episode of pancreatitis, however 62% (8/13) with abnormalities was their first time tested. We identified obesity and having severe acute pancreatitis (SAP) during the prior AP episode to testing could be associated with abnormal glucose. We propose that systematic screening for abnormal glucose after the first episode of acute pancreatitis in order to better establish the timing of diabetes progression.

Cardiovascular Consequences of Childhood Secondhand Tobacco Smoke Exposure: Prevailing Evidence, Burden, and Racial and Socioeconomic Disparities: A Scientific Statement From the American Heart Association.

BACKGROUND: Although public health programs have led to a substantial decrease in the prevalence of tobacco smoking, the adverse health effects of tobacco smoke exposure are by no means a thing of the past. In the United States, 4 of 10 school-aged children and 1 of 3 adolescents are involuntarily exposed to secondhand tobacco smoke (SHS), with children of minority ethnic backgrounds and those living in low-socioeconomic-status households being disproportionately affected (68% and 43%, respectively). Children are particularly vulnerable, with little control over home and social environment, and lack the understanding, agency, and ability to avoid SHS exposure on their own volition; they also have physiological or behavioral characteristics that render them especially susceptible to effects of SHS. Side-stream smoke (the smoke emanating from the burning end of the cigarette), a major component of SHS, contains a higher concentration of some toxins than mainstream smoke (inhaled by the smoker directly), making SHS potentially as dangerous as or even more dangerous than direct smoking. Compelling animal and human evidence shows that SHS exposure during childhood is detrimental to arterial function and structure, resulting in premature atherosclerosis and its cardiovascular consequences. Childhood SHS exposure is also related to impaired cardiac autonomic function and changes in heart rate variability. In addition, childhood SHS exposure is associated with clustering of cardiometabolic risk factors such as obesity, dyslipidemia, and insulin resistance. Individualized interventions to reduce childhood exposure to SHS are shown to be at least modestly effective, as are broader-based policy initiatives such as community smoking bans and increased taxation. PURPOSE: The purpose of this statement is to summarize the available evidence on the cardiovascular health consequences of childhood SHS exposure; this will support ongoing efforts to further reduce and eliminate SHS exposure in this vulnerable population. This statement reviews relevant data from epidemiological studies, laboratory-based experiments, and controlled behavioral trials concerning SHS and cardiovascular disease risk in children. Information on the effects of SHS exposure on the cardiovascular system in animal and pediatric studies, including vascular disruption and platelet activation, oxidation and inflammation, endothelial dysfunction, increased vascular stiffness, changes in vascular structure, and autonomic dysfunction, is examined. CONCLUSIONS: The epidemiological, observational, and experimental evidence accumulated to date demonstrates the detrimental cardiovascular consequences of SHS exposure in children. IMPLICATIONS: Increased awareness of the adverse, lifetime cardiovascular consequences of childhood SHS may facilitate the development of innovative individual, family-centered, and community health interventions to reduce and ideally eliminate SHS exposure in the vulnerable pediatric population. This evidence calls for a robust public health policy that embraces zero tolerance of childhood SHS exposure.

The Impact of Concomitant Left Ventricular Non-compaction with Congenital Heart Disease on Perioperative Outcomes.

Left ventricular non-compaction (LVNC) is a heterogeneous myocardial disorder characterized by prominent trabeculations and inter-trabecular recesses which may occur in association with congenital heart disease (CHD). To date, few studies have been performed to assess whether the concomitant diagnosis of LVNC affects the outcomes of CHD surgery. A retrospective review of patients with LVNC with CHD (LVNC-CHD), 0-5 years of age, was conducted. Patients with CHD without LVNC (CHD-only) and 0-5 years of age with similar diagnosis distribution were selected for comparison. Perioperative data, including CHD diagnosis, operative course, and postoperative complications were collected and compared between groups. LVNC-CHD was diagnosed in 26 children. Of the 26 with LVNC-CHD, 20 underwent surgery and these patients were compared with 276 CHD-only controls. Median total length of stay in the hospital was 12.5 days (IQR 5.5-63 days) in LVNC-CHD compared to 5 days (IQR 3-10 days) in CHD-only (p < 0.005). Postoperative death, cardiac arrest, or need for ECMO or transplantation occurred in 6/20 (30 %) of the LVNC-CHD patients compared to 3/276 (1 %) of the CHD-only group (p < 0.0001). LVNC-CHD patients had significantly longer hospital length of stay and higher perioperative complications compared to CHD-only patients without myocardial abnormalities. Pediatric cardiac care teams should be cognizant of the possibility of the increased perioperative risk associated with concomitant LVNC. Future prospective studies are warranted.

Adolescent oligomenorrhea (age 14-19) tracks into the third decade of life (age 20-28) and predicts increased cardiovascular risk factors and metabolic syndrome.

OBJECTIVE: Assess whether adolescent oligomenorrhea (age 14-19) tracks into young adulthood (age 20-28) and predicts increased cardiometabolic risk factors, metabolic syndrome (MetS), and impaired fasting glucose-type II diabetes mellitus (IFG+T2DM). MATERIALS AND METHODS: Prospective study of menstrual cyclicity and its metabolic effects in 865 black and white schoolgirls from age 9 to 19, and 605 of these 865 girls from age 20 to 28. MAIN FINDINGS: Patterns of menstrual delays (oligomenorrhea) during ages 14-19 and ages 20-28 were closely related (p<.0001). Adolescent menses delay (ages 14-19, p<.0001), mean insulin (ages 20-28, p=.0003), and self-identified polycystic ovary syndrome (PCOS, p=.049) predicted ages 20-28 menses delay. Menses delays during ages 14-19 and 20-28, and, their interaction product were correlated with IFG+T2DM and MetS at ages 20-28. Waist circumference (ages 20-28, p<.0001), mean triglyceride (ages 20-28, p=.005), and the number of average menstrual cycles≥42 days (ages 20-28, p=.04) predicted IFG+T2DM (ages 20-28). MetS (ages 9-19, p<.0001), mean insulin (ages 20-28, p=.0002), the number of ≥42 day gaps between menstrual periods (ages 20-28, p=.02), and cigarette smoking at age 18-19 (p=.04) were significant explanatory variables for MetS at ages 27-28. As MetS status category changed from age 14-19 to 27-28 from best to worst: (no → no), (yes → no), (yes → yes), (no → yes), the number of women with ≥2 menses delays during ages 20-28 rose from 3% to 4% to 15% to 17%, p=.0001. MetS status change from age 9-19 to 27-28 was positively associated with mean insulin (age 20-28, p<.0001), cigarette smoking (age 24-25, p=.01) and the number of menses delays during ages 20-28 (p=.04). PRINCIPAL CONCLUSIONS: Menstrual patterns track from adolescence to young adulthood, and oligomenorrhea predicts MetS and IFG+T2DM. Patterns of menses delays in adolescence should be considered as a significant risk factor for future development of young adult IFG+T2DM, MetS, oligomenorrhea, and polycystic ovary syndrome.

Maxillary hypoplasia in the cleft patient: contribution of orthodontic dental space closure to orthognathic surgery.

BACKGROUND: Cleft lip and palate surgery in the developing child is known to be associated with maxillary hypoplasia. However, the effects of nonsurgical manipulations on maxillary growth have not been well investigated. The authors present the contribution of orthodontic dental space closure with canine substitution to maxillary hypoplasia and the need for orthognathic surgery. METHODS: Cleft lip/palate and cleft palate patients older than 15 years of age were reviewed for dental anomalies, orthodontic canine substitution, and Le Fort I advancement. Skeletal relationships of the maxilla to the skull base (SNA), mandible (ANB), and facial height were determined on lateral cephalograms. Logistic regression analyses were performed to estimate odds ratios. RESULTS: Ninety-five patients were reviewed (mean age, 18.1 years). In 65 patients with congenitally missing teeth, 55 percent with patent dental spaces required Le Fort I advancement. In contrast, 89 percent who underwent canine substitution required Le Fort I advancement (p = 0.004). Canine substitution is associated with a statistically significant increase in maxillary retrognathia when compared with dental space preservation on lateral cephalograms (mean SNA, 75.2 and 79.0, respectively; p = 0.006). Adjusting for missing dentition, logistic regression analyses demonstrated that canine substitution is an independent predictor for orthognathic surgery (OR, 6.47) and maxillary retrusion defined by SNA < 78 (OR, 8.100). CONCLUSIONS: The coordination of orthodontia and surgery is essential to cleft care. The authors report a strong association between orthodontic cleft closure using canine substitution with maxillary hypoplasia and subsequent Le Fort I advancement, and suggest systematic criteria for management of cleft-related dental agenesis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Childhood lifestyle and clinical determinants of adult ideal cardiovascular health: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Princeton Follow-Up Study.

BACKGROUND: The American Heart Association recently defined ideal cardiovascular health by simultaneous presence of seven health behaviors and factors. The concept is associated with cardiovascular disease incidence, and cardiovascular disease and all-cause mortality. To effectively promote ideal cardiovascular health already early in life, childhood factors predicting future ideal cardiovascular health should be investigated. Our aim was thus to comprehensively explore childhood determinants of adult ideal cardiovascular health in population based cohorts from three continents. METHODS: The sample comprised a total of 4409 participants aged 3-19 years at baseline from the Cardiovascular Risk in Young Finns Study (YFS; N = 1883) from Finland, Childhood Determinants of Adult Health Study (CDAH; N = 1803) from Australia and Princeton Follow-up Study (PFS; N = 723) from the United States. Participants were re-examined 19-31 years later when aged 30-48 years. RESULTS: In multivariable analyses, independent childhood predictors of adult ideal cardiovascular health were family socioeconomic status (P < 0.01; direct association) and BMI (P < 0.001; inverse association) in all cohorts. In addition, blood pressure (P = 0.007), LDL-cholesterol (P < 0.001) and parental smoking (P = 0.006) in the YFS, and own smoking (P = 0.001) in CDAH were inversely associated with future ideal cardiovascular health. CONCLUSIONS: Among several lifestyle and clinical indicators studied, higher family socioeconomic status and non-smoking (parental/own) in childhood independently predict ideal cardiovascular health in adulthood. As atherosclerotic cardiovascular diseases are rooted in childhood, our findings suggest that special attention could be paid to children who are from low socioeconomic status families, and who smoke or whose parents smoke, to prevent cardiovascular disease morbidity and mortality.

Risk factors for cardiovascular disease and type 2 diabetes retained from childhood to adulthood predict adult outcomes: the Princeton LRC Follow-up Study.

BACKGROUND: Pediatric risk factors predict adult cardiovascular disease (CVD) and type 2 diabetes (T2DM), but whether they predict events independently of adult risk factors is not fully known. OBJECTIVE: Assess whether risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood. STUDY DESIGN: 770 schoolchildren, ages 5-20 (mean age 12), 26-yr prospective follow-up. We categorized childhood and adult risk factors and 26-year changes (triglycerides [TG], LDL cholesterol, BMI, blood pressure [BP] and glucose ≥, and HDL cholesterol < pediatric and young adult cutoffs). These risk factors and race, cigarette smoking, and family history of CVD and T2DM were assessed as predictors of CVD and T2DM at mean age 38. RESULTS: Children who had high TG and retained high TG as adults had increased CVD events as adults (p = .0005). Children who had normal BMI and retained normal BMI as adults had reduced CVD events as adults (p = .02). Children who had high BP or high TG and retained these as adults had increased T2DM as adults (p = .0006, p = .003). CONCLUSIONS: Risk factors for CVD and T2DM retained from childhood to adulthood predict CVD and T2DM in young adulthood and support universal childhood screening.

Dietary assessment of adolescents undergoing laparoscopic Roux-en-Y gastric bypass surgery: macro- and micronutrient, fiber, and supplement intake.

BACKGROUND: Extremely obese adolescents are increasingly undergoing bariatric procedures, which restrict dietary intake. However, as yet, no data are available describing the change in caloric density or composition of the adolescent bariatric patient's diet pre- and postoperatively. Our objective was to assess the 1-year change in the dietary composition of adolescents undergoing bariatric surgery at a tertiary care children's hospital. METHODS: A total of 27 subjects (67% female, 77% white, age 16.7 ± 1.4 yr, baseline body mass index 60.1 ± 14.1 kg/m(2)) were prospectively enrolled into an observational cohort study 1 month before undergoing laparoscopic Roux-en-Y gastric bypass from August 2005 to March 2008. The 3-day dietary intake was recorded at baseline (n = 24) and 2 weeks (n = 16), 3 months (n = 11), and 1 year (n = 9) postoperatively. The dietary record data were verified by structured interview and compared with the Dietary Reference Intake values for ages 14-18 years. RESULTS: By 1 year after surgery, the mean caloric intake, adjusted for body mass index was 1015 ± 182 kcal/d, a 35% reduction from baseline. The proportion of fat, protein, and carbohydrate intake did not differ from baseline. However, the protein intake was lower than recommended postoperatively. The calcium and fiber intake was also persistently lower than recommended. Calcium and vitamin B(12) supplementation increased the likelihood of meeting the daily minimal recommendations (P ≤ .02). CONCLUSION: At 1 year after Roux-en-Y gastric bypass, the adolescents' caloric intake remained restricted, with satisfactory macronutrient composition but a lower than desirable intake of calcium, fiber, and protein.

Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass.

OBJECTIVES: We investigated the temporal pattern and predictive value (alone and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein [L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated acute kidney injury (AKI). BACKGROUND: Serum creatinine (S(Cr)) is a delayed marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI biomarkers could allow early intervention and improve outcomes. METHODS: Data from 220 pediatric patients were analyzed. Urine samples were obtained before and at intervals after CPB initiation. AKI was defined as a ≥50% increase in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker elevation was established, and biomarker elevations were correlated with AKI severity and clinical outcomes. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement, and integrated discrimination improvement. RESULTS: AKI occurred in 27% of patients. Urine NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18 and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations were correlated with AKI severity and clinical outcomes and improved AKI prediction above a clinical model. At 2 h, addition of NGAL increased the AUC from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p < 0.05). The added predictive ability of the biomarkers was supported by net reclassification improvement and integrated discrimination improvement. Biomarker combinations further improved AKI prediction. CONCLUSIONS: Urine NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and are correlated with disease severity and clinical outcomes after pediatric CPB. These biomarkers, particularly in combination, may help establish the timing of injury and allow earlier intervention in AKI.