Offspring BMI Research Articles

Factors Associated With Weight, Length, and BMI Change in Adolescents' Offspring in Their First Year of Life.

Background: Young maternal age is associated with negative outcomes at birth and with offspring's growth. In low- and middle-income countries, adolescents' offspring growth little has been studied.Objective: To determine the association of maternal sociodemographic characteristics with weight, length, and BMI change in adolescents' offspring in their first year of life.Methods: This is a one-year follow-up study that included adolescent mothers and their offspring from 2010 to 2017. The infant anthropometric variables were performed at birth, 3, 6, and 12 months. Maternal health, pregnancy, and social variables were evaluated as well as birth outcomes. Crude, percentage, Z score, and percentile changes of weight, length, and BMI were evaluated from birth to 1-year-old. Statistical analyses were adjusted by maternal chronological age, socioeconomic status, breastfeeding duration, the timing of introduction of complementary feeding, among other variables.Results: We examined 186 dyads (mother-infant). The median maternal age was 15.5 years, and the mean pre-pregnancy BMI was 20. The mean gestational age was 39.1 weeks for infants, birth weight was 3,039 g, and length at birth was 49.5-cm. Maternal chronological age, the timing of introduction of complementary feeding, socioeconomic status, and maternal occupation were associated with offspring's weight gain at 12 months. Length gain was associated with exclusive breastfeeding. Socioeconomic status and occupation were associated with offspring's BMI change. When performing adjusted multivariable analyses, weight and length at birth were associated weight and BMI at 12 months.Conclusions: Weight at birth may negatively predict infant's weight and BMI changes at 12 months, while length at birth may positively predict the changes. Maternal chronological age, socioeconomic level, occupation, and the timing of the introduction of complementary feeding were associated with the weight change. Only exclusive breastfeeding was associated with length Z-score change in adolescents' offspring in their first 12-months of life.

Associations of maternal diet and nutritional status with offspring hepatic steatosis in the Avon longitudinal study of parents and children

BackgroundPriming for cardiometabolic diseases, including non-alcoholic fatty liver disease (NAFLD), is hypothesized to begin in utero. The primary objective of this study is to determine whether there is an association between maternal nutritional status and offspring NAFLD.MethodsData come from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK. The analytic sample included 3353 participants who had maternal information on pre-pregnancy BMI, gestational weight gain, diabetes, and free sugar intake as percent of total energy and were assessed for mild-severe hepatic steatosis at 24 years by transient elastography (controlled attenuation parameter score ≥ 248 dB/m). Multiple logistic regression was used to evaluate the association between maternal factors and offspring hepatic steatosis at 24 years.ResultsIn confounder-adjusted models the independent associations for each maternal factor with mild to severe vs low hepatic steatosis at 24 years were: pre-pregnancy overweight (OR: 1.84, 95%CL: 1.43–2.38) or obesity (OR: 2.73, 95%CL: 1.84–4.03), more than recommended gestational weight gain (OR: 1.30, 95%CL: 1.04–1.64), diabetes (OR: 1.39, 95%CI: 0.87, 2.21), and high free sugar intake during pregnancy (OR: 1.04, 95% CI: 0.82, 1.33). These associations were largely mediated by BMI at 24 years, but not by birthweight or breastfeeding.ConclusionsOur results suggest that maternal nutritional status is associated with the development of NAFLD in their adult offspring, although the relationship is largely mediated by offspring BMI in adulthood.

Genetic Interactions with Intrauterine Diabetes Exposure in Relation to Obesity: The EPOCH and Project Viva Studies.

To examine whether BMI-associated genetic risk variants modify the association of intrauterine diabetes exposure with childhood BMI z-scores, we assessed the interaction between 95 BMI-associated genetic variants and in utero exposure to maternal diabetes among 459 children in the Exploring Perinatal Outcomes among Children historical prospective cohort study (n = 86 exposed; 373 unexposed) in relation to age- and sex-standardized childhood BMI z-scores (mean age = 10.3 years, standard deviation = 1.5 years). For the genetic variants showing a nominally significant interaction, we assessed the relationship in an additional 621 children in Project Viva, which is an independent longitudinal cohort study, and used meta-analysis to combine the results for the two studies. Seven of the ninety-five genetic variants tested exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to the offspring BMI z-score in EPOCH. Five of the seven variants exhibited a consistent direction of interaction effect across both EPOCH and Project Viva. While none achieved statistical significance in the meta-analysis after accounting for multiple testing, three variants exhibited a nominally significant interaction with in utero exposure to maternal diabetes in relation to offspring BMI z-score: rs10733682 near LMX1B (interaction β = 0.39; standard error (SE) = 0.17), rs17001654 near SCARB2 (β = 0.53; SE = 0.22), and rs16951275 near MAP2K5 (β = 0.37; SE = 0.17). BMI-associated genetic variants may enhance the association between exposure to in utero diabetes and higher childhood BMI, but larger studies of in utero exposures are necessary to confirm the observed nominally significant relationships.

Association between parental and offspring BMI: results from EPACI Portugal 2012.

To assess the longitudinal association between parental BMI and offspring's BMI, in EPACI Portugal 2012. Longitudinal study with retrospective collection of children's anthropometry data since birth. Children's anthropometric data were gathered from individual child health bulletins, and parents' anthropometrics were self-reported. Children's and parents' BMI were classified according to WHO cut-offs. Linear mixed models with random intercept and slope for age were applied to quantify the association between parental BMI and children BMI Z-score (zBMI). EPACI Portugal 2012. Representative sample from the Portuguese population (n 2230) aged from 12 to 36 months. 58·9 % of the fathers and 35·6 % of the mothers were overweight (OW) or obese. Prevalence of infants who were, at least, at risk of OW increased from 17·0 % to 30·3 % since birth to 12 months. About half of the mothers with pre-pregnancy OW and obesity (OB) gained gestational weight above the recommendations. The children from mothers with gestational weight gain (GWG) below the recommendations showed a -0·15 SD lower zBMI (95 % CI -0·23, -0·06) in early life, comparing with mothers within GWG recommendations. Children of obese mothers were more likely to present a higher zBMI (0·24 SD, 95 % CI 0·13, 0·35) throughout the first months of life. A high prevalence of OW and OB was observed in Portuguese young adults and toddlers. Mothers' pre-pregnancy BMI and insufficient GWG had a direct effect on offspring BMI. Early effective interventions are needed in order to prevent the transgenerational transmission of OB.

Prenatal exposure to maternal stressful life events and earlier age at menarche: the Raine Study.

Is there an association between prenatal exposure to stressful life events and age at menarche, and does childhood BMI mediate this association? Girls exposed to prenatal stress had a slightly earlier age at menarche, but this association did not show a dose-response effect and was not mediated by childhood offspring BMI. Prenatal stress may impact on reproductive function in females including age at menarche, but human data are very limited. High childhood BMI is known to be associated with earlier age at menarche. Only one small study has measured the association between maternal stress and age at menarche and reported that childhood BMI mediated the association between maternal stress and earlier age at menarche. However, neither maternal stress nor age at menarche was prospectively recorded and the study was limited to 31 mother-daughter pairs. The Raine Study is a large prospective population-based pregnancy cohort study (n = 1414 mother-daughter pairs) continuously followed from prenatal life through to adolescence. In the present study, we examined the association between exposure to maternal stressful life events during early, late and total gestation and age at menarche in offspring using 753 mother-daughter pairs with complete case information. Mothers prospectively reported stressful life events during pregnancy at 18 and 34 weeks using a standardized 10-point questionnaire. Exact date of menarche was assessed using a purpose-designed questionnaire at 8, 10, 14 and 17 years of age. Complete information on exposure, outcome and confounding variables was obtained from 753 mothers-daughter pairs. Multivariate linear regression complete case analysis was used to examine associations between maternal stressful life event exposure and age at menarche. Potential selection bias was evaluated using multiple imputations (50 datasets). The mediating effects of offspring childhood BMI (ages 5, 8, or 10 years) on these associations were measured in separate sub-analyses. Most (580/753, 77%) daughters were exposed to at least one prenatal stressful life event. Exposure to maternal stressful life events during the entire pregnancy was associated with a non-linear earlier age at menarche. Exposure to one event and two or more psychological stressful events was associated with a 3.5 and 1.7-month earlier onset of puberty, respectively when compared to the reference group with no exposure maternal stressful life events. The estimates from multiple imputation with 50 datasets were comparable with complete case analysis confirming the existence of an underlying effect. No separate significant effects were observed for exposure during early or late gestation. The association between prenatal stressful events and age at menarche was not mediated by childhood BMI in the offspring. Stressful life events may have affected pregnant women in different ways and self-perceived maternal stress severity may have provided a more precise estimate of gestational psychological stress. The observed non-linear U-shape of the association between maternal psychological stress and age at menarche did not reflect a dose-response. This suggests that the first exposure to prenatal stress exerts a greater effect on fetal reproductive development. A potential mechanism is via dramatic initial activation of the hypothalamic-pituitary-adrenal (HPA) axis following the first stressful life event which is greater than that observed following subsequent exposure to two or more maternal stressful life events. Whilst we adjusted for a priori chosen confounders, we cannot exclude residual confounding or confounding by factors we did not include. Maternal age at menarche was not available so the effects of familial history/genetics could not be assessed. There was a large loss due to the number of girls with no information on date of menarche and missing confounder information implying risk of selection bias and multiple imputation analyses did not fully exclude this risk (similar direction but slightly weaker estimate magnitude). Menarche is a sentinel reproductive event and earlier age at menarche carries implications for psychological, social and reproductive health and for long-term risk of common non-communicable diseases. Understanding the factors regulating age at menarche has extensive health implications. This is the first population-based cohort study in humans to demonstrate that prenatal psychological stress might directly modify age at menarche. Dr. Bräuner and Trine Koch's salaries were supported by Doctor Sofus Carl Emil Friis and spouse Olga Doris Friis foundation, The Danish Cancer Society (Kræftens Bekæmpelse, RP15468, R204-A12636, Denmark) and The Danish Health Foundation (Helsefonden, F-22181-23, Denmark). Martha Hickey was funded by NHMRC Practitioner Fellowships. The funding bodies played no role in the design, collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Dr. Hart has received personal fees in his function as the Medical Director of Fertility Specialists of Western Australia and received educational sponsorship grants from MSD, Merck-Serono and from Ferring Pharmaceuticals. Dr Hart has also received personal fees from Shareholders in Western IVF outside the submitted work. NA.

Associations of maternal early-pregnancy dietary glycemic index with childhood general, abdominal and ectopic fat accumulation

SummaryBackground & aimsMaternal hyperglycemia during pregnancy is an important risk factor for childhood adiposity. Maternal dietary glycemic index during pregnancy directly influences maternal and fetal glucose concentrations. We examined the associations of maternal early-pregnancy dietary glycemic index with offspring general, abdominal and ectopic fat accumulation among normal weight and overweight or obese pregnant women and their offspring.MethodsIn a population-based cohort study among 2488 Dutch pregnant women and their children, we assessed maternal dietary glycemic index by food frequency questionnaire at median 13.4 (95% range 10.7; 21.1) weeks gestation. Dietary glycemic index was used continuously and categorized into low (≤55), normal (56–69) and high (≥70) glycemic index diet. We measured offspring BMI, total fat mass and android/gynoid fat mass ratio by DXA, and visceral fat mass and liver fat fraction by MRI at 10 years.ResultsNo associations of maternal early-pregnancy dietary glycemic index with offspring adiposity were present among normal weight women and their children. Among overweight and obese women and their children, 1-Standard Deviation Score (SDS) increase in maternal early-pregnancy dietary glycemic index was associated with higher childhood BMI (0.10 SDS, 95% Confidence Interval (CI) 0.01; 0.19), total fat mass index (0.13 SDS, 95% CI 0.05; 0.22), visceral fat mass index (0.19 SDS, 95% CI 0.07; 0.32) and tended to be associated with a higher android/gynoid fat mass ratio (0.09 SDS, 95% CI −0.01; 0.19) and higher risk of childhood overweight (Odds Ratio (OR) 1.20, 95% CI 0.97; 1.48). Overweight and obese women consuming an early-pregnancy low-glycemic index diet, as compared to an early-pregnancy normal-glycemic index diet, had children with lower BMI, total fat mass index, visceral fat mass index and android/gynoid fat mass ratio at 10 years (p-values<0.05). No women consumed a high-glycemic index diet. No associations were explained by maternal socio-economic, lifestyle and dietary characteristics, birth or childhood characteristics. No associations with liver fat fraction were present.ConclusionsIn overweight or obese women and their children, a higher maternal early-pregnancy dietary glycemic index is associated with childhood general, abdominal and visceral fat accumulation, but not with liver fat. Intervention studies among overweight and obese pregnant women may need to target the dietary glycemic index to prevent childhood adiposity.

Lifestyle Intervention in Pregnant Women With Obesity Impacts Cord Blood DNA Methylation, Which Associates With Body Composition in the Offspring.

Maternal obesity may lead to epigenetic alterations in the offspring and might thereby contribute to disease later in life. We investigated whether a lifestyle intervention in pregnant women with obesity is associated with epigenetic variation in cord blood and body composition in the offspring. Genome-wide DNA methylation was analyzed in cord blood from 208 offspring from the Treatment of Obese Pregnant women (TOP)-study, which includes pregnant women with obesity randomized to lifestyle interventions comprised of physical activity with or without dietary advice versus control subjects (standard of care). DNA methylation was altered at 379 sites, annotated to 370 genes, in cord blood from offspring of mothers following a lifestyle intervention versus control subjects (false discovery rate [FDR] <5%) when using the Houseman reference-free method to correct for cell composition, and three of these sites were significant based on Bonferroni correction. These 370 genes are overrepresented in gene ontology terms, including response to fatty acids and adipose tissue development. Offspring of mothers included in a lifestyle intervention were born with more lean mass compared with control subjects. Methylation at 17 sites, annotated to, for example, DISC1, GBX2, HERC2, and HUWE1, partially mediates the effect of the lifestyle intervention on lean mass in the offspring (FDR <5%). Moreover, 22 methylation sites were associated with offspring BMI z scores during the first 3 years of life (P < 0.05). Overall, lifestyle interventions in pregnant women with obesity are associated with epigenetic changes in offspring, potentially influencing the offspring’s lean mass and early growth.

Influence of maternal pre-pregnancy nutritional status on offspring anthropometric measurements and body composition in three Brazilian Birth Cohorts.

We aimed at evaluating the association of maternal pre-pregnancy nutritional status with offspring anthropometry and body composition. We also evaluated whether these associations were modified by gender, diet and physical activity and mediated by birth weight. Birth cohort study. Waist circumference was measured with an inextensible tape, and fat and lean mass were measured using dual-energy X-ray absorptiometry. Multiple linear regression was used to adjust for possible confounders and allele score of BMI. We carried out mediation analysis using G-formula. In 1982, 1993 and 2004, all maternity hospitals in Pelotas (South Brazil) were visited daily and all live births whose families lived in the urban area of the city were evaluated. These subjects have been followed up at different ages. Offspring of obese mothers had on average higher BMI, waist circumference and fat mass index than those of normal weight mothers, and these differences were higher among daughters. The magnitudes of the association were similar in the cohorts, except for height, where the association pattern was not clear. In the 1982 cohort, further adjustment for a BMI allele score had no material influence on the magnitude of the associations. Mediation analyses showed that birth weight captured part of this association. Our findings suggest that maternal pre-pregnancy nutritional status is positively associated with offspring BMI and adiposity in offspring. And this association is higher among daughters whose mother was overweight or obese and, birth weight explains part of this association.

Body mass index trajectories up to preschool age in a multi-ethnic population; relations with maternal gestational diabetes, BMI and gestational weight gain.

Independent effects of gestational diabetes (GDM), maternal prepregnant obesity and gestational weight gain on offspring BMI and obesity are scarcely documented. We examined associations between GDM and children's BMI trajectories from birth to 4-5years age, and effects of prepregnant obesity and gestational weight gain not mediated through GDM. We included 734 children from a population-based, multi-ethnic cohort of women and their offspring followed from early pregnancy. All women were screened for GDM. Using linear mixed models, we explored associations between maternal factors and children's BMI development through seven serial measurements. At birth and age 4-5years, BMI of children exposed to GDM was similar to those not exposed. However, they had slower BMI growth (B=-0.1BMI units/month (95% CI: -0.17, -0.04)) during first 6months, and faster BMI growth from 6months to 4-5years. Maternal prepregnant obesity was associated with higher child BMI at birth, and thereafter persistently higher BMI. High gestational weight gain was associated with faster BMI growth from 6months to 4-5years. Effects of maternal GDM, prepregnant obesity, and gestational weight gain on children's BMI and BMI trajectories from birth to preschool age differed in relation to effect size, timing and direction.

Childhood Obesity and Device-Measured Sedentary Behavior: An Instrumental Variable Analysis of 3,864 Mother-Offspring Pairs.

Intergenerational data on mother-offspring pairs were utilized in an instrumental variable analysis to examine the longitudinal association between BMI and sedentary behavior. The sample included 3,864 mother-offspring pairs from the 1970 British Cohort Study. Height and weight were recorded in mothers (age 31 [5.4] years) and offspring (age 10 years) and repeated in offspring during adulthood. Offspring provided objective data on sedentary behavior (7-day thigh-worn activPAL) in adulthood at age 46 to 47 years. Maternal BMI, the instrumental variable, was associated with offspring BMI at age 10 (change per kg/m2 , β = 0.11; 95% CI: 0.09 to 0.12), satisfying a key assumption of instrumental variable analyses. Offspring (change per kg/m2 , β = 0.010; 95% CI: -0.02 to 0.03 h/d) and maternal BMI (β = 0.017; 95% CI: 0.001 to 0.03 h/d) was related to offspring sedentary time, suggestive of a causal impact of BMI on sedentary behavior (two-stage least squares analysis, β = 0.18 [SE 0.08], P = 0.015). For moderate-vigorous physical activity, there were associations with offspring BMI (β = -0.010; 95% CI: -0.017 to -0.004) and maternal BMI (β = -0.007; 95% CI: -0.010 to -0.003), with evidence for causality (two-stage least squares analysis, β = -0.060 [SE 0.02], P = 0.001). There is strong evidence for a causal pathway linking childhood obesity to greater sedentary behavior.

Associations of Gestational Weight Gain Rate During Different Trimesters with Early-Childhood Body Mass Index and Risk of Obesity.

This study aimed to estimate the associations of gestational weight gain rate (GWGR) during different trimesters with offspring growth and overweight/obesity risk. The study included 4,807 mother-infant pairs enrolled in Wuhan, China. GWGR in each trimester was used as a continuous and a categorical variable to estimate the associations with offspring BMI z score (ZBMI) and overweight/obesity risk between 0 and 2 years. Greater GWGR (per 0.2 kg/wk) in the first, second, and third trimester was positively associated with offspring ZBMI across birth to 2 years old (β 0.06 [95% CI: 0.04-0.09], β 0.13 [95% CI: 0.09-0.16], and β 0.04 [95% CI: 0.02-0.07], respectively). Excessive GWGR in the first trimester (≥ 0.30 kg/wk) was associated with an odds ratio (OR) of 1.58 (95% CI: 1.18-2.13) and 1.37 (95% CI: 1.11-1.71) for macrosomia and 2-year overweight/obesity, respectively. Excessive GWGR in the second trimester was associated with an OR of 2.09 (95% CI: 1.42-3.08), 1.21 (95% CI: 1.02-1.43), and 1.48 (95% CI: 1.15-1.90) for macrosomia, 1-year, and 2-year overweight/obesity, respectively. Excessive GWGR in the third trimester was associated with an OR of 1.91 (95% CI: 1.27-2.86) and 1.32 (95% CI: 1.02-1.72) for macrosomia and 2-year overweight/obesity, respectively. Excessive GWGR in each trimester was positively associated with offspring ZBMI and early-childhood overweight/obesity risk.

Associations between a maternal healthy lifestyle score and adverse offspring birth outcomes and childhood obesity in the Lifeways Cross-Generation Cohort Study

Maternal adherence to healthy lifestyle behaviors during pregnancy has been associated with reduced risk of obesity in the offspring. Our objective is to examine associations between a composite healthy lifestyle score (HLS) in expectant mothers and adverse offspring birth outcomes and childhood obesity. The Lifeways Study comprises 665 mother-child pairs. A composite HLS (scored 0-5) based on high dietary quality (top 40% of the Healthy Eating Index (HEI)-2015), moderate to vigorous physical activity (MVPA), healthy pre-pregnancy BMI (18.5-24.9 kg/m2), never smoker, and no/moderate alcohol intake was calculated. Birth outcomes were abstracted from hospital records. Offspring waist circumference (WC) and BMI was determined at age 5 and 9. Logistic regression tested HLS associations with offspring outcomes. Offspring birth weight, length, and head circumference were positively associated with the maternal HLS (p < 0.001), whereas child BMI and incidence of overweight/obesity at age 5 and 9 were negatively associated (p < 0.05). In multivariable models, a lower maternal HLS was associated with increased risk of low birth weight (LBW) (P trend = 0.04) and lower likelihood of macrosomia (P trend = 0.03). Examined individually, poor maternal dietary quality, smoking, and alcohol intake were associated with higher risk of LBW (p < 0.04). Likelihood of macrosomia and combined overweight/obesity at age 5 and 9 years were greater among mothers with a pre-pregnancy BMI in the range with obesity (p < 0.04). Smoking during pregnancy was also linked to greater risk of childhood overweight/obesity (OR:1.91, 95% CI:1.01-3.61, p = 0.04 at age 5 and OR: 2.14, 95% CI:1.01-4.11, p = 0.03 at age 9). Our findings suggest that maternal adherence to a healthy lifestyle during pregnancy, in particular having a good quality diet, not smoking, and no/low alcohol intake in combination with a healthy pre-pregnancy BMI, is associated with reduced risk of adverse offspring birth outcomes and childhood obesity.

Sex-dependent associations of maternal androgen levels with offspring BMI and weight trajectory from birth to early childhood.

In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. Higher maternal androgen levels associated with lower BMIz at birth (β = -0.39, 95% CI: -0.73, -0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = -0.72, 95% CI: -1.40, -0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Associations of Maternal Non-Nutritive Sweetener Intake During Pregnancy with Childhood BMI Trajectory

Abstract Objectives To examine the extent to which non-nutritive sweetener (NNS; e.g., aspartame) intake during pregnancy is associated with offspring BMI z-score trajectory from birth to 15 years. Methods We included 1683 mother-child pairs from Project Viva, a prospective pre-birth-cohort recruited in 1999–2002 in Massachusetts. The main exposure was maternal NNS intake assessed in the 1st and 2nd trimesters of pregnancy using a food frequency questionnaire. We defined NNS as servings/day of diet soda + NutraSweet (aspartame packets) averaged across 1st and 2nd trimesters. We used linear regression models to examine associations of maternal NSS intake with offspring BMI z-score at each in-person research visit (birth, 6 months, 3 years, 7 years, and 12 years). We also used mixed-effects models to examine associations with BMI z-score trajectory from birth to 15 years, including both research and clinical measures of BMI for 1570 participants with ≥3 BMI z-score values. We adjusted all models for maternal pre-pregnancy BMI, age, race/ethnicity, education, parity, and pregnancy smoking status. Results 70% of mothers were white and mean (SD) pre-pregnancy BMI was 24.6 (5.2) kg/m2. Mean (SD; IQR) intake of NNS was 0.23 (0.55; 0.22) servings/day. While maternal NNS intake (per servings/day) was not associated with BMI z-score at birth (β −0.03 units; 95% CI −0.14, 0.08), NNS was associated with higher BMI z-score at 6 months (β 0.17; 0.06, 0.28), 3 years (β 0.13; 0.03, 0.24), 7 years (β 0.16; 0.04, 0.29) and 12 years (β 0.16; 0.01, 0.31). Based on the BMI z-score trajectory, the associations of NNS intake (Q4 vs. Q1) with BMI z-score became stronger with increasing age from 3–14 years (pinteraction with age: &amp;lt;0.01); e.g., 3 years (β 0.13; 0.02, 0.23), 7 years (β 0.24; 0.11, 0.37) and 12 years (β 0.38; 0.20, 0.57). Conclusions Our findings showed higher maternal NNS intake during pregnancy was associated with higher BMI z-score from childhood to early adolescence, and the associations strengthened with increasing age. Funding Sources US National Institutes of Health (R01 HD034568, UH3 OD023286).

M127. BODY MASS INDEX IN THE MIDDLE-AGED OFFSPRING OF PARENTS WITH SEVERE MENTAL ILLNESS

BackgroundThe prevalence of obesity is increasing public health problem with significant costs. Elevated risk for obesity is reported in patients with severe mental illness. People with obesity have an increased risk for a number of common medical conditions, including type 2 diabetes, cardiovascular disease, coronary heart disease, dyslipidemia and hypertension. The increased physical illness may be associated with unhealthy lifestyles such as smoking, substance use, often with inadequate access to health services. Still, very is known about the comorbidity of SMI and obesity in families. We explored the association between parental severe mental illness and BMI in middle-aged offspring. Our hypothesis was that offspring of people with severe mental illness have increased risk for obesity.MethodsThe Northern Finland Birth Cohort 1966 is cohort study of offspring with expected date of birth in 1966. The final study sample included 5,467 middle-aged offspring. We used parental severe mental illness as exposure in the study. BMI measured.at the age of 46 years was classified in for categories: underweight (BMI below 18.5), normal range (BMI 18.5–24.9), overweight (BMI 25.0–29.9), obese class I (BMI 30.0–34.9) and obese class II-III (BMI 35 or more). We used mothers’ marital status, smoking, educational level and offspring’ place of birth as confounders.ResultsRisk for obesity was elevated in offspring of mothers with SMI (overweight: adjusted OR 1.81 (1.25–2.63), obese class I: 1.71 (1.08–2.73), obese class II-III: 2.36 (1.35–4.13)). For offspring of fathers with SMI the results were not statistically significant (overweight: adjusted OR 0.94 (0.70–1.26), obese class I: 1.42 (1.00–2.00), obese class II-III: 0.89 (0.51–1.56)).DiscussionAccording to our knowledge, this is the first study of BMI in adult offspring of parents with severe mental illness. We found an elevated risk of obesity in the middle-aged offspring of mothers with SMI. The findings support our hypothesis of higher morbidity from obesity in offspring of parents with SMI. We found an elevated risk of substantially increased BMI in the middle-aged offspring of mothers with SMI. However, we did not find elevated risk of increased BMI in the middle-aged offspring of fathers with SMI and when examining the offspring of either parent with SMI. This means that there might be a common familial pathway leading to co-occurrence of obesity and SMI.

Long-Term Effects of Intrauterine Exposure to Antidepressants on Physical, Neurodevelopmental, and Psychiatric Outcomes: A Systematic Review.

Reviews on child outcomes following in utero antidepressant exposure have focused on short-term outcomes. However, several recent individual studies reported on adverse physical, neurodevelopmental, and psychiatric outcomes beyond infancy and early childhood. The objective of this systematic review was to establish the long-term effects of prenatal antidepressant exposure on physical, neurodevelopmental, and psychiatric outcomes in individuals aged 4 years and older. Embase, MEDLINE Ovid, Web of Science, Cochrane Central, and Google Scholar were systematically searched for all relevant articles, written in English and published prior to November 8, 2018, using terms describing antidepressants, pregnancy, and developmental outcomes. All original research articles on long-term outcomes of prenatal antidepressant exposure were eligible for inclusion. After screening and removal of duplicates, a total of 34 studies were identified. Included articles were qualitatively analyzed to determine inconsistency, indirectness, imprecision, and study bias. The identified studies demonstrated statistically significant associations between prenatal antidepressant exposure and a range of physical, neurodevelopmental, and psychiatric outcomes. Yet, the risk of confounding by indication was high. When controlling for confounders, 5 studies investigating physical outcomes (asthma, cancer, body mass index [BMI], epilepsy) found no association except conflicting outcomes for BMI. Eighteen studies examining neurodevelopmental outcomes (cognition, behavior, IQ, motor development, speech, language, and scholastic outcomes) found no consistent associations with antidepressant exposure after taking confounders into account. Eleven studies investigated psychiatric outcomes. After adjusting for confounders, prenatal antidepressant exposure was associated with affective disorders but not with childhood psychiatric outcomes (eg, autism spectrum disorders, attention-deficit/hyperactivity disorder). Reported associations between in utero exposure to antidepressants and physical, neurodevelopmental, and psychiatric outcomes, in large part, seem to be driven by the underlying maternal disorder. When limiting confounding by indication, prenatal exposure to antidepressants was significantly associated only with offspring BMI and affective disorders.

Association Between Maternal Prepregnancy Body Mass Index and Anthropometric Parameters, Blood Pressure, and Retinal Microvasculature in Children Age 4 to 6 Years

Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has previously been associated with offspring cardiometabolic risk factors, such as fat mass, glucose and insulin levels, and blood pressure, but these associations appear to be largely mediated by offspring BMI. To our knowledge, no studies have assessed alterations in the retinal microvasculature in association with maternal prepregnancy BMI. To investigate the association between maternal prepregnancy BMI and anthropometric parameters, blood pressure, and retinal vessel parameters in children age 4 to 6 years. Participants included mother-child pairs of the population-based Environmental Influence on Early Aging (ENVIRONAGE) birth cohort study (Flanders, Belgium) who were recruited at birth from February 2010 to June 2014 and followed-up at age 4 to 6 years between October 2014 and July 2018. Data were analyzed from February 2019 to April 2019. Maternal prepregnancy BMI based on height and weight measurements at the first antenatal visit (weeks 7-9 of gestation). Children's anthropometric, blood pressure, and retinal microcirculation measurements at age 4 to 6 years. Retinal vessel diameters and the tortuosity index, a measure for the curvature of the retinal vasculature, were obtained by fundus image analysis. This study included 240 mothers and children with a mean (SD) age of 29. 9 (4.2) years and 54.8 (4.7) months, respectively. Of these, 114 children (47.5%) were boys. Maternal prepregnancy BMI was positively associated with the child's birth weight, BMI, waist circumference, blood pressure, and retinal vessel tortuosity. A 1-point increase in maternal prepregnancy BMI was associated with a 0.26-mm Hg (95% CI, 0.08-0.44) higher mean arterial pressure for their children, with similar estimates for systolic and diastolic blood pressure. Independent from the association with blood pressure, a 1-point increase in maternal prepregnancy BMI was associated with a 0.40 (95% CI, 0.01-0.80) higher retinal tortuosity index (× 103). The hypothesis that these associations reflect direct intrauterine mechanisms is supported by the following observations: associations were independent of the current child's BMI and the estimates for paternal BMI at the follow-up visit did not reach significance. Considering that blood pressure tracks from childhood into adulthood and microvascular changes may be early markers of cardiometabolic disease development, our results suggest that maternal prepregnancy BMI is an important modifiable risk factor for later-life cardiovascular health of the offspring.

Increased leptin, decreased adiponectin and FGF21 concentrations in adolescent offspring of women with gestational diabetes.

Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence. The follow-up study included 504 GDM and 540 control offspring aged 9-16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays. GDM offspring had 38% (95% CI: 22-55%) higher leptin, 0.6 mg/L (95% CI: -1.2, -0.04 mg/L) lower adiponectin, and 32% (95% CI: -47%, -12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage. GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

Determinants of intramyocellular lipid accumulation in early childhood

Background/ObjectivesAccumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood.Subjects/MethodsThis study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6.ResultsThe mean IMCL level at 4.5 years was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B = 0.396 (0.069, 0.724); p = 0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B = 0.065 (0.001, 0.128); p = 0.045) and conditional relative weight gain between ages 2 and 3 (B = 0.052 (0.012, 0.093); p = 0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B = 0.028 (0.012, 0.044); p = 0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6.ConclusionThis study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.

358-OR: Adiponectin, Leptin, and FGF-21 Levels in Adolescents Exposed and Not Exposed to Gestational Diabetes—Results from the Danish National Birth Cohort

Background: Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic diseases. Adipokines such as adiponectin and leptin may be involved in the underlying mechanisms. Fibroblast growth factor 21 (FGF-21) has recently been identified as a potent metabolic regulator. Therefore, we investigated the impact of fetal exposure to GDM on adiponectin, leptin and FGF-21 levels and their associations with metabolic and adiposity traits during adolescence. Methods: A prospective study comparing 502 offspring of GDM exposed mothers and 535 offspring of non-exposed mothers. During a clinical exam of offspring, aged 9-16 years old, metabolic traits were measured and fasting blood samples collected and assayed for serum concentrations of leptin, adiponectin and FGF-21. Results: GDM exposed offspring had 34% (95% CI: 18-51%) higher leptin levels, and 34% (95% CI: -48, -15%) lower FGF-21 concentrations than non-exposed offspring (p&amp;lt;0.05), but no significant differences in adiponectin concentrations were found. These differences remained significant after adjusting for major confounders, including maternal pre-pregnancy BMI. Offspring leptin concentrations correlated positively with insulin and HOMA-IR, whereas adiponectin concentrations were inversely correlated (p&amp;lt;0.05). Elevated leptin and decreased adiponectin concentrations correlated with all measures of adiposity, whereas FGF-21 correlated with total fat percentage only. In analyses stratified by offspring BMI z-score categories, GDM exposure had no significant effect on leptin and adiponectin concentrations. Conclusion: GDM exposed offspring had higher leptin and lower FGF-21 concentrations than non-exposed controls, but this was driven by higher prevalence of adiposity among GDM offspring. The differential adipokine concentration does not seem to be the major driver behind the dysmetabolic phenotype among GDM offspring. Disclosure F.B. Kampmann: None. A. Thuesen: None. L. Hjort: None. M. Bjerre: None. J. Frystyk: None. I. Tetens: None. A.A. Bjerregaard: None. J.E. Chavarro: None. S.F. Olsen: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. A.A. Vaag: Employee; Self; AstraZeneca. L. Grunnet: None. Funding Danish Council for Strategic Research; Innovation Fund, Denmark (09-067124, 11-115923); Novo Nordisk Foundation (NNF160C0022518); Danish Diabetes Academy