Associations of early childhood body mass index trajectories with body composition and cardiometabolic markers at age 10 years: the Ethiopian infant anthropometry and body composition (iABC) birth cohort study.

BACKGROUND: Variability in body mass index (BMI) (kg/m2) trajectories is associated with body composition and cardiometabolic markers in early childhood, but it is unknown how these associations track to later childhood. OBJECTIVES: We aimed to assess associations of BMI trajectories from 0 to 5 y with body composition and cardiometabolic markers at 10 y. METHODS: In the Ethiopian infant anthropometry and body composition (iABC) birth cohort, we previously identified 4 distinct BMI trajectories from 0 to 5 y: stable low BMI (19.2%), normal BMI (48.8%), rapid growth to high BMI (17.9%), and slow growth to high BMI (14.1%). At 10 y, we obtained data from 320 children on anthropometry, body composition, abdominal subcutaneous and visceral fat, and cardiometabolic markers. Associations of BMI trajectories and 10-y outcomes were analyzed using multiple linear regression. RESULTS: Compared with children with the normal BMI trajectory, those with rapid growth to high BMI had 1.7 cm (95% CI: 0.1, 3.3) larger waist circumference and those with slow growth to high had 0.63 kg/m2 (95% CI: 0.09, 1.17) greater fat mass index and 0.19 cm (95% CI: 0.02, 0.37) greater abdominal subcutaneous fat, whereas those with stable low BMI had -0.28 kg/m2 (95% CI: -0.59, 0.03) lower fat-free mass at 10 y. Although the confidence bands were wide and included the null value, children with rapid growth to high BMI trajectory had 48.6% (95% CI: -1.4, 123.8) higher C-peptide concentration and those with slow growth to high BMI had 29.8% (95% CI: -0.8, 69.8) higher insulin and 30.3% (95% CI: -1.1, 71.6) higher homeostasis model assessment of insulin resistance, whereas those with rapid growth to high BMI had -0.23 mmol/L (95% CI: -0.47, 0.02) lower total cholesterol concentration. The trajectories were not associated with abdominal visceral fat, blood pressure, glucose, and other lipids at 10 y. CONCLUSIONS: Children with rapid and slow growth to high BMI trajectories before 5 y tend to show higher measures of adiposity and higher concentrations of markers related to glucose metabolism at 10 y. CLINICAL TRIAL REGISTRY: ISRCTN46718296 (https://www.isrctn.com/ISRCTN46718296).

Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort.

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants. METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark's registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers. TRIAL REGISTRATION NUMBER: NCT05166447.

Effects of relaxation interventions during pregnancy on maternal mental health, and pregnancy and newborn outcomes: A systematic review and meta-analysis.

BACKGROUND: Stress during pregnancy is detrimental to maternal health, pregnancy and birth outcomes and various preventive relaxation interventions have been developed. This systematic review and meta-analysis aimed to evaluate their effectiveness in terms of maternal mental health, pregnancy and birth outcomes. METHOD: The protocol for this review is published on PROSPERO with registration number CRD42020187443. A systematic search of major databases was conducted. Primary outcomes were maternal mental health problems (stress, anxiety, depression), and pregnancy (gestational age, labour duration, delivery mode) and birth outcomes (birth weight, Apgar score, preterm birth). Randomized controlled trials or quasi-experimental studies were eligible. Meta-analyses using a random-effects model was conducted for outcomes with sufficient data. For other outcomes a narrative review was undertaken. RESULT: We reviewed 32 studies comprising 3,979 pregnant women aged 18 to 40 years. Relaxation interventions included yoga, music, Benson relaxation, progressive muscle relaxation (PMR), deep breathing relaxation (BR), guided imagery, mindfulness and hypnosis. Intervention duration ranged from brief experiment (~10 minutes) to 6 months of daily relaxation. Meta-analyses showed relaxation therapy reduced maternal stress (-4.1 points; 95% Confidence Interval (CI): -7.4, -0.9; 9 trials; 1113 participants), anxiety (-5.04 points; 95% CI: -8.2, -1.9; 10 trials; 1965 participants) and depressive symptoms (-2.3 points; 95% CI: -3.4, -1.3; 7 trials; 733 participants). Relaxation has also increased offspring birth weight (80 g, 95% CI: 1, 157; 8 trials; 1239 participants), explained by PMR (165g, 95% CI: 100, 231; 4 trials; 587 participants) in sub-group analysis. In five trials evaluating maternal physiological responses, relaxation therapy optimized blood pressure, heart rate and respiratory rate. Four trials showed relaxation therapy reduced duration of labour. Apgar score only improved significantly in two of six trials. One of three trials showed a significant increase in birth length, and one of three trials showed a significant increase in gestational age. Two of six trials examining delivery mode showed significantly increased spontaneous vaginal delivery and decreased instrumental delivery or cesarean section following a relaxation intervention. DISCUSSION: We found consistent evidence for beneficial effects of relaxation interventions in reducing maternal stress, improving mental health, and some evidence for improved maternal physiological outcomes. In addition, we found a positive effect of relaxation interventions on birth weight and inconsistent effects on other pregnancy or birth outcomes. High quality adequately powered trials are needed to examine impacts of relaxation interventions on newborns and offspring health outcomes. CONCLUSION: In addition to benefits for mothers, relaxation interventions provided during pregnancy improved birth weight and hold some promise for improving newborn outcomes; therefore, this approach strongly merits further research.

Heterogeneity in glycaemic control in children and adolescents with type 1 diabetes: A latent class trajectory analysis of Danish nationwide data.

AIMS: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors. METHODS: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling. RESULTS: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region. CONCLUSIONS: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed.

The Associations of Breastfeeding Status at 6 Months with Anthropometry, Body Composition, and Cardiometabolic Markers at 5 Years in the Ethiopian Infant Anthropometry and Body Composition Birth Cohort.

(1) Background: Breastfeeding (BF) has been shown to lower the risk of overweight and cardiometabolic disease later in life. However, evidence from low-income settings remains sparse. We examined the associations of BF status at 6 months with anthropometry, body composition (BC), and cardiometabolic markers at 5 years in Ethiopian children. (2) Methods: Mother-child pairs from the iABC birth cohort were categorised into four BF groups at 6 months: 1. "Exclusive", 2. "Almost exclusive", 3. "Predominantly" and 4. "Partial or none". The associations of BF status with anthropometry, BC, and cardiometabolic markers at 5 years were examined using multiple linear regression analyses in three adjustment models. (3) Results: A total of 306 mother-child pairs were included. Compared with "Exclusive", the nonexclusive BF practices were associated with a lower BMI, blood pressure, and HDL-cholesterol at 5 years. Compared with "Exclusive", "Predominantly" and "Almost exclusive" had shorter stature of -1.7 cm (-3.3, -0.2) and -1.2 cm (-2.9, 0.5) and a lower fat-free mass index of -0.36 kg/m2 (-0.71, -0.005) and -0.38 kg/m2 (-0.76, 0.007), respectively, but a similar fat mass index. Compared with "Exclusive", "Predominantly" had higher insulin of 53% (2.01, 130.49), "Almost exclusive" had lower total and LDL-cholesterol, and "Partial or none" had a lower fat mass index. (5) Conclusions: Our data suggest that children exclusively breastfed at 6 months of age are overall larger at 5 years, with greater stature, higher fat-free mass but similar fat mass, higher HDL-cholesterol and blood pressure, and lower insulin concentrations compared with predominantly breastfed children. Long-term studies of the associations between BF and metabolic health are needed to inform policies.

Growth and Body Composition 5 y After Treatment for Severe Acute Malnutrition: A 5-y Prospective Matched Cohort Study in Ethiopian Children.

BACKGROUND: Short-term anthropometric outcomes are well documented for children treated for severe acute malnutrition (SAM). However, anthropometric recovery may not indicate restoration of healthy body composition. OBJECTIVES: This study aimed to evaluate long-term associations of SAM with growth and body composition of children 5 y after discharge from community-based management of acute malnutrition (CMAM). METHODS: We conducted a 5-y prospective cohort study, enrolling children aged 6 to 59 mo discharged from CMAM (post-SAM) (n = 203) and nonmalnourished matched controls (n = 202) from Jimma Zone, Ethiopia in 2013. Anthropometry and body composition (bioelectrical impedance) were assessed. Multiple linear regression models tested differences in height-for-age (HAZ), weight-for-age (WAZ), and body mass index-for-age (BAZ) z-scores; height-adjusted fat-free mass index (FFMI); and FM index (FMI) between groups. RESULTS: Post-SAM children had higher stunting prevalence than controls at discharge (82.2% compared with 36.0%; P < 0.001), 1 y (80.2% compared with 53.7%; P < 0.001), and 5 y postdischarge (74.2% compared with 40.8%; P < 0.001). Post-SAM children remained 5 cm shorter throughout follow-up, indicating no HAZ catch-up. No catch-up in WAZ or BAZ was observed. Post-SAM children had lower hip (-2.05 cm; 95% CI: -2.73, -1.36), waist (-0.92 cm; CI: -1.59, -0.23) and mid-upper arm (-0.64 cm; CI: -0.90, -0.42) circumferences and lower-limb length (-1.57 cm; 95% CI: -2.21, -0.94) at 5 y postdischarge. They had larger waist-hip (0.02 cm; 95% CI: 0.008, 0.033) and waist-height (0.013 cm; 95% CI: 0.004, 0.021) ratios, and persistent deficits in FFMI at discharge and 6 mo and 5 y postdischarge (P < 0.001 for all). No difference was detected in head circumference, sitting height, or FMI. CONCLUSIONS: Five y after SAM treatment, children maintained deficits in HAZ, WAZ, BAZ, and FFMI, with preservation of FMI, sitting height, and head circumference at the expense of lower-limb length, indicating a "thrifty growth" pattern. Research is urgently needed to identify effective clinical and public health interventions to mitigate these consequences of malnutrition.

Large Language Models for Epidemiological Research via Automated Machine Learning: Case Study Using Data From the British National Child Development Study.

Background: Large language models have had a huge impact on natural language processing (NLP) in recent years. However, their application in epidemiological research is still limited to the analysis of electronic health records and social media data. objectives: To demonstrate the potential of NLP beyond these domains, we aimed to develop prediction models based on texts collected from an epidemiological cohort and compare their performance to classical regression methods. Methods: We used data from the British National Child Development Study, where 10,567 children aged 11 years wrote essays about how they imagined themselves as 25-year-olds. Overall, 15% of the data set was set aside as a test set for performance evaluation. Pretrained language models were fine-tuned using AutoTrain (Hugging Face) to predict current reading comprehension score (range: 0-35) and future BMI and physical activity (active vs inactive) at the age of 33 years. We then compared their predictive performance (accuracy or discrimination) with linear and logistic regression models, including demographic and lifestyle factors of the parents and children from birth to the age of 11 years as predictors. Results: NLP clearly outperformed linear regression when predicting reading comprehension scores (root mean square error: 3.89, 95% CI 3.74-4.05 for NLP vs 4.14, 95% CI 3.98-4.30 and 5.41, 95% CI 5.23-5.58 for regression models with and without general ability score as a predictor, respectively). Predictive performance for physical activity was similarly poor for the 2 methods (area under the receiver operating characteristic curve: 0.55, 95% CI 0.52-0.60 for both) but was slightly better than random assignment, whereas linear regression clearly outperformed the NLP approach when predicting BMI (root mean square error: 4.38, 95% CI 4.02-4.74 for NLP vs 3.85, 95% CI 3.54-4.16 for regression). The NLP approach did not perform better than simply assigning the mean BMI from the training set as a predictor. Conclusions: Our study demonstrated the potential of using large language models on text collected from epidemiological studies. The performance of the approach appeared to depend on how directly the topic of the text was related to the outcome. Open-ended questions specifically designed to capture certain health concepts and lived experiences in combination with NLP methods should receive more attention in future epidemiological studies.

Association of linear growth velocities between 0 and 6 years with kidney function and size at 10 years: A birth cohort study in Ethiopia.

BACKGROUND: Risk of noncommunicable diseases accrues from fetal life, with early childhood growth having an important role in adult disease risk. There is a need to understand how early-life growth relates to kidney function and size. OBJECTIVES: This study aimed to assess the association of linear growth velocities among children between 0 and 6 y with kidney function and size among children aged 10 y. METHODS: The Ethiopian Anthropometric and Body Composition birth cohort recruited infants born at term to mothers living in Jimma with a birth weight of ≥1500 g and without congenital malformations. Participants were followed up with 13 measurements between birth and 6 y of age. The latest follow-up was at ages 7-12 y with measurement of serum cystatin C as a marker of kidney function and ultrasound assessment of kidney dimensions. Kidney volume was computed using an ellipsoid formula. Linear-spline multilevel modeling was used to compute linear growth velocities between 0 and 6 y. Multiple linear regression modeling was used to examine the associations of linear growth velocities in selected age periods with cystatin C and kidney size. RESULTS: Data were captured from 355 children, at a mean age of 10 (range 7-12) y. The linear growth velocity was high between 0 and 3 mo and then decreased with age. There was no evidence of an association of growth velocity ≤24 mo with cystatin C at 10 y. Between 24 and 48 and 48 and 76 mo, serum cystatin C was higher by 2.3% [95% confidence interval (CI): 0.6, 4.2] and 2.1% (95% CI: 0.3, 4.0) for 1 SD higher linear growth velocity, respectively. We found a positive association between linear growth velocities at all intervals between 0 and 6 y and kidney volume. CONCLUSIONS: Greater linear growth between 0 and 6 y of development was positively associated with kidney size, and greater growth velocity after 2 y was associated with higher serum cystatin C concentrations.

Associations of weight and body composition at birth with body composition and cardiometabolic markers in children aged 10 y: the Ethiopian infant anthropometry and body composition birth cohort study.

BACKGROUND: Although birth weight (BW) has been associated with later cardiovascular disease and type 2 diabetes, the role of birth fat mass (BFM) and birth fat-free mass (BFFM) on cardiometabolic health is unclear. OBJECTIVES: To examine associations of BW, BFM, and BFFM with later anthropometry, body composition, abdominal fat, and cardiometabolic markers. METHODS: Birth cohort data on standardized exposure variables (BW, BFM, and BFFM) and follow-up information at age 10 y on anthropometry, body composition, abdominal fat, and cardiometabolic markers were included. A linear regression analysis was used to assess associations of exposures with outcome variables, adjusting for maternal and child characteristics at birth and current body size in separate models. RESULTS: Among 353 children, mean (SD) age was 9.8 (1.0) y, and 51.5% were boys. In the fully adjusted model, 1-SD higher BW and BFFM were associated with 0.81 cm (95% CI: 0.21, 1.41 cm) and 1.25 cm (95% CI: 0.64, 1.85 cm) greater height at 10 y, respectively. The 1-SD higher BW and BFM were associated with 0.32 kg/m2 (95% CI: 0.14, 0.51 kg/m2) and 0.42 kg/m2 (95% CI: 0.25, 0.59 kg/m2) greater fat mass index at 10 y, respectively. In addition, 1-SD higher BW and BFFM were associated with 0.22 kg/m2 (95% CI: 0.09, 0.34 kg/m2) greater FFM index, whereas a 1-SD greater BFM was associated with a 0.05 cm greater subcutaneous adipose tissue (95% CI: 0.01, 0.11 cm). Furthermore, 1-SD higher BW and BFFM were associated with 10.3% (95% CI: 1.4%, 20.0%) and 8.3% (95% CI: -0.5%, 17.9%) greater insulin, respectively. Similarly, 1-SD higher BW and BFFM were associated with 10.0% (95% CI: 0.9%, 20.0%) and 8.5% (95% CI: -0.6%, 18.5%) greater homeostasis model assessment of insulin resistance, respectively. CONCLUSIONS: BW and BFFM rather than BFM are predictors of height and FFM index at 10 y. Children with higher BW and BFFM showed higher insulin concentrations and homeostasis model assessment of insulin resistance at 10 y of age. This trial was registered at ISRCTN as ISRCTN46718296.

Low birthweight is associated with a higher incidence of type 2 diabetes over two decades independent of adult BMI and genetic predisposition.

AIMS/HYPOTHESIS: Low birthweight is a risk factor for type 2 diabetes. Most previous studies are based on cross-sectional prevalence data, not designed to study the timing of onset of type 2 diabetes in relation to birthweight. We aimed to examine associations of birthweight with age-specific incidence rate of type 2 diabetes in middle-aged to older adults over two decades. METHODS: Adults aged 30-60 years enrolled in the Danish Inter99 cohort in 1999-2001 (baseline examination), with information on birthweight from original birth records from 1939-1971 and without diabetes at baseline, were eligible. Birth records were linked with individual-level data on age at diabetes diagnosis and key covariates. Incidence rates of type 2 diabetes as a function of age, sex and birthweight were modelled using Poisson regression, adjusting for prematurity status at birth, parity, polygenic scores for birthweight and type 2 diabetes, maternal and paternal diabetes history, socioeconomic status and adult BMI. RESULTS: In 4590 participants there were 492 incident type 2 diabetes cases during a mean follow-up of 19 years. Type 2 diabetes incidence rate increased with age, was higher in male participants, and decreased with increasing birthweight (incidence rate ratio [95% CI per 1 kg increase in birthweight] 0.60 [0.48, 0.75]). The inverse association of birthweight with type 2 diabetes incidence was statistically significant across all models and in sensitivity analysis. CONCLUSIONS/INTERPRETATION: A lower birthweight was associated with increased risk of developing type 2 diabetes independent of adult BMI and genetic risk of type 2 diabetes and birthweight.

Body Mass Index Trajectories in Children Exposed to Gestational Diabetes in Utero: A Nationwide Register-based Study.

CONTEXT: Children exposed to gestational diabetes mellitus (GDM) in utero are at high risk of developing overweight and obesity, but their postnatal growth trajectories and risk profiles remain unclear. OBJECTIVE: We aimed to identify distinct body mass index (BMI) trajectories from birth to 10 years of age in children exposed to GDM and to explore their associations with infant and maternal characteristics. METHODS: This nationwide cohort study linked data from Danish registries on 15 509 children exposed to GDM in utero, born in Denmark from January 2008 to October 2019. We applied latent class trajectory modeling to identify distinct BMI trajectories. Associations of BMI trajectories with infant and maternal characteristics were analyzed using multiple linear regression. RESULTS: We identified 3 distinct BMI trajectories characterized by a "normal" (60%), a "late accelerating" (28%) and an "early accelerating" (12%) BMI trajectory, the 2 latter at risk of overweight and obesity, respectively, at age 10 years, relative to World Health Organization child growth standards. Children in the "late accelerating" BMI trajectory were more often born large for gestational age (P < .001). More children in the "early accelerating" BMI trajectory were boys, born small for gestational age, and had mothers with a higher pre-pregnancy BMI compared to the other groups (P < .001). CONCLUSION: Children exposed to GDM in utero differ widely in their BMI trajectory. The detection of risk profiles based on early BMI growth and infant and maternal characteristics provides an opportunity for future targeted care and prevention.

Understanding the child mortality decline in Guinea-Bissau: the role of population-level nutritional status measured by mid-upper arm circumference.

BACKGROUND: Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children's MUAC. METHODS: This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003-05) and a late period (2014-16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education. RESULTS: A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality. CONCLUSIONS: From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow's interventions.

Trajectory and predictors of HbA1c in children and adolescents with type 1 diabetes-A Danish nationwide cohort study.

OBJECTIVES: Poor glycemic control in type 1 diabetes increases the risk of chronic complications and it is essential to identify life periods and predictors associated with deteriorating HbA1c . The aim was to describe specific HbA1c trajectories in Danish children and adolescents with type 1 diabetes and study associations with clinical and sociodemographic factors. RESEARCH DESIGN AND METHODS: 5889 children with type 1 diabetes were included from the nationwide Danish Registry of Childhood and Adolescent Diabetes with annual visits during 1996-2019. Trajectories of HbA1c were modeled with linear mixed-effects models (using age as time scale, included as cubic spline) and with an individual-specific random intercept and slope. The following cofactors were included stepwise into the model: sex, age at diagnosis, calendar year, parental education, immigrant status, health care region, blood glucose monitoring (BGM) frequency, treatment modalities: continuous subcutaneous insulin infusion (pump) versus multiple daily insulin injection therapy (pen) and continuous glucose monitoring. RESULTS: HbA1c overall increased during age while there was a significant decreasing secular trend. Older age at diagnosis was associated with a steeper trajectory, and non-Danish origin and shorter parental education were each associated with higher levels of HbA1c across age. A lower BGM frequency was associated with a markedly poorer HbA1c trajectory, while no significant differences were shown for different treatment modalities. CONCLUSIONS: Glycemic outcome worsened with age during childhood and adolescence, which is of clinical concern. Important predictors for a poorer glycemic trajectory were later age at diabetes diagnosis, shorter parental education, non-Danish origin and, in particular low BGM frequency.

Smoking in pregnancy is associated with increased adiposity and retinal arteriolar wall-to-lumen ratio in adolescence: The Copenhagen Child Cohort Study 2000.

PURPOSE: To investigate the association between prenatal exposures and anthropometric data and cardiovascular risk factors including retinal arteriolar wall-to-lumen ratio in adolescence. METHODS: This longitudinal observational study included all 1445 adolescents from the Copenhagen Child Cohort 2000 who attended the 2016-2017 examination. Outcome measures included retinal arteriolar wall-to-lumen ratio, height, body mass index, waist-to-hip ratio, body composition measured by bioimpedance, and blood pressure. Information on prenatal exposures (birth weight, gestational age, maternal smoking during pregnancy) as well as sex, parental age, household income and parental educational levels were obtained from national registries. Associations between exposures and outcome measures were analyzed using general linear models. RESULTS: Maternal smoking during pregnancy was associated with a higher retinal arteriolar wall-to-lumen ratio (0.004 or 1.9%, P = 0.009) at age 16/17 years, an association driven exclusively by the female participants (0.008 or 3.7%, P < 0.0001). Maternal smoking during pregnancy was also associated to higher body-mass index (1.43 kg/m2, P < 0.0001), waist-to-hip ratio (0.02, P < 0.0001) and fat mass index (0.93 kg/m2, P < 0.0001). Birth weight, gestational age, and parental age had no detectable impact on retinal arteriolar wall-to-lumen ratios. CONCLUSION: Prenatal exposure to tobacco smoking is associated with a higher risk of obesity and, predominantly in girls, to a greater retinal arteriolar wall thickness, which suggests that maternal smoking may induce an unfavorable cardiovascular and metabolic risk profile in the child.

Need for improved diabetes support among people with psychiatric disorders and diabetes treated in psychiatric outpatient clinics: results from a Danish cross-sectional study.

INTRODUCTION: People with psychiatric disorders have increased risk of premature death partly due to diabetes. This study aims to explore the quality of diabetes care, diabetes management, diabetes support and well-being of people with psychiatric disorders and diabetes. RESEARCH DESIGN AND METHODS: A total of 107 participants aged ≥18 years with diabetes and psychiatric disorders treated at psychiatric outpatient clinics in Denmark were recruited from August 2018 to June 2019. This descriptive cross-sectional study includes data from medical records on quality of diabetes care (eg, level and annual examination of hemoglobin A1c (HbA1c)) and questionnaires on diabetes management (measured on items from the Summary of Diabetes Self-Care Activities Scale and diabetes distress based on Problem Areas in Diabetes Scale (PAID-5)), diabetes support (no, some or high support from eight potential support persons and experience of care actions measured on items from Patient Assessment of Chronic Illness Care) and well-being (WHO 5-Item Scale and self-rated general health). RESULTS: The mean age was 52 years, 56% were men, the mean body mass index was 31.9 kg/m2, the median HbA1c was 53 mmol/mol (7.0%) and the mean blood pressure was 131/83 mm Hg. The proportion with annual measurements of HbA1c was 93%, blood pressure 80%, cholesterol 93%, foot examination 77% and eye examination 75%. Fifty-one per cent had high diabetes distress (PAID-5 score ≥8). Diabetologists and general practitioners (39% and 37%) were the health professionals most frequently reported to provide high diabetes support. CONCLUSIONS: This study highlights a need for improved diabetes support in people with psychiatric disorders and diabetes. Although a high proportion received appropriate diabetes care, we found high levels of diabetes distress, moderate levels of optimal self-management behaviors, low well-being and low diabetes support from psychiatric health professionals, while one-third of the population found it relevant to receive diabetes support from psychiatric health professionals.

The double burden of malnutrition: aetiological pathways and consequences for health.

Malnutrition has historically been researched and addressed within two distinct silos, focusing either on undernutrition, food insecurity, and micronutrient deficiencies, or on overweight, obesity, and dietary excess. However, through rapid global nutrition transition, an increasing proportion of individuals are exposed to different forms of malnutrition during the life course and have the double burden of malnutrition (DBM) directly. Long-lasting effects of malnutrition in early life can be attributed to interconnected biological pathways, involving imbalance of the gut microbiome, inflammation, metabolic dysregulation, and impaired insulin signalling. Life-course exposure to early undernutrition followed by later overweight increases the risk of non-communicable disease, by imposing a high metabolic load on a depleted capacity for homoeostasis, and in women increases the risk of childbirth complications. These life-course trajectories are shaped both by societal driving factors-ie, rapidly changing diets, norms of eating, and physical activity patterns-and by broader ecological factors such as pathogen burden and extrinsic mortality risk. Mitigation of the DBM will require major societal shifts regarding nutrition and public health, to implement comprehensive change that is sustained over decades, and scaled up into the entire global food system.

Body mass index trajectories in early childhood in relation to cardiometabolic risk profile and body composition at 5 years of age.

BACKGROUND: Both impaired and accelerated postnatal growth have been associated with adult risks of obesity and cardiometabolic diseases, like type 2 diabetes and cardiovascular disease. However, the timing of the onset of cardiometabolic changes and the specific growth trajectories linking early growth with later disease risks are not well understood. OBJECTIVES: The aim of this study was to identify distinct trajectories of BMI growth from 0 to 5 y and examine their associations with body composition and markers of cardiometabolic risk at age 5 y. METHODS: In a prospective birth cohort study of 453 healthy and term Ethiopian children with BMIs assessed a median of 9 times during follow-up, we identified subgroups of distinct BMI trajectories in early childhood using latent class trajectory modeling. Associations of the identified growth trajectories with cardiometabolic markers and body composition at 5 y were analyzed using multiple linear regression analyses in 4 adjustment models for each outcome. RESULTS: We identified 4 heterogeneous BMI growth trajectories: stable low BMI (19.2%), normal BMI (48.8%), rapid catch-up to high BMI (17.9%), and slow catch-up to high BMI (14.1%). Compared with the normal BMI trajectory, children in the rapid catch-up to high BMI trajectory had higher triglycerides (TGs) (range of ß-coefficients in Models 1-4: 19-21%), C-peptides (23-25%), fat masses (0.48-0.60 kg), and fat-free masses (0.50-0.77 kg) across the 4 adjustment models. Children in the stable low BMI trajectory had lower LDL cholesterol concentrations (0.14-0.17 mmol/L), HDL cholesterol concentrations (0.05-0.09 mmol/L), fat masses (0.60-0.64 kg), and fat-free masses (0.35-0.49 kg), but higher TGs (11-13%). CONCLUSIONS: The development of obesity and cardiometabolic risks may be established already in early childhood; thus, our data provide a further basis for timely interventions targeted at young children from low-income countries with unfavorable growth patterns. The birth cohort was registered at ISRCTN as ISRCTN46718296.

Associations of fat mass and fat-free mass accretion in infancy with body composition and cardiometabolic risk markers at 5 years: The Ethiopian iABC birth cohort study.

BACKGROUND: Accelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years. METHODS AND FINDINGS: Healthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0-3 and 3-6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0-3 and 3-6 months was associated with 339 g (95% CI: 243-435 g, p < 0.001) and 367 g (95% CI: 250-484 g, p < 0.001) greater FM at 5 years, respectively. Higher FM at birth and FM accretion from 0 to 3 months were associated with higher FFM and cholesterol concentrations at 5 years. Associations for cholesterol were strongest for low-density lipoprotein (LDL)-cholesterol, and remained significant after adjusting for current FM. A 100-g higher FM at birth and 100-g/month higher FM accretion from 0 to 3 months were associated with 0.16 mmol/l (95% CI: 0.05-0.26 mmol/l, p = 0.005) and 0.06 mmol/l (95% CI: 0.01-0.12 mmol/l, p = 0.016) higher LDL-cholesterol at 5 years, respectively. Higher FFM at birth and FFM accretion in infancy were associated with higher FM, FFM, waist circumference, and height at 5 years. For instance, 100-g/month higher FFM accretion in the periods 0-3 and 3-6 months was associated with 1,002 g (95% CI: 815-1,189 g, p < 0.001) and 624 g (95% CI: 419-829 g, p < 0.001) greater FFM at 5 years, respectively. We found no associations of FM and FFM growth with any of the other studied cardiometabolic markers including glucose, HbA1c, insulin, C-peptide, HOMA-IR, triglycerides, and blood pressure. Non-attendance at the 5-year follow-up visit was the main limitation of this study, which may have introduced selection bias and limited the power of the regression analyses. CONCLUSIONS: FM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years.

Higher Weight and Weight Gain after 4 Years of Age Rather than Weight at Birth Are Associated with Adiposity, Markers of Glucose Metabolism, and Blood Pressure in 5-Year-Old Ethiopian Children.

BACKGROUND: Fetal and early life growth is associated with adult risk of obesity and cardiometabolic disease. However, little is known about the relative importance of birth weight and successive periods of weight gain on markers of cardiometabolic risk in childhood in low-income populations. OBJECTIVES: The objective was to study associations of birth weight and weight gain velocities in selected age intervals from birth to 60 mo with height, fat-free mass (FFM), and markers of adiposity and cardiometabolic risk at 60 mo. METHODS: In a prospective cohort study of 375 Ethiopian children aged 60 mo, we estimated individual weight gain velocities in the periods between birth and 3, 6, 24, 48, and 60 mo using linear-spline mixed-effects modeling. Subsequently, we analyzed associations of birth weight, weight gain velocities, and current weight with height, FFM, and markers of adiposity and cardiometabolic risk. RESULTS: Weight gain from 48 to 60 mo and weight at 60 mo rather than birth weight were the strongest correlates of insulin, C-peptide, HOMA-IR, blood pressure, height, FFM, waist circumference, and fat mass at 60 mo. For instance, 1 SD higher (1 SD = 50 g/mo) weight accretion from 48 to 60 mo was associated with a higher insulin of 23.3% (95% CI: 9.6%, 38.8%), C-peptide of 11.4% (2.7%, 20.8%), systolic blood pressure of 1.4 mm Hg (0.6, 2.3 mm Hg), fat mass of 0.72 kg (0.59, 0.85 kg), and FFM of 0.70 kg (0.56, 0.85 kg). Weight gain from 0 to 3 mo was positively associated with LDL cholesterol, systolic blood pressure, height, and the body composition indices, and weight gain from 24 to 48 mo was inversely associated with blood glucose. CONCLUSIONS: In 60-mo-old Ethiopian urban children, weight gain and weight after 48 mo rather than weight at birth may represent a sensitive period for variations in markers of adiposity and glucose metabolism. The birth cohort is registered at https://www.isrctn.com/ as ISRCTN46718296.