Infant Adiposity Research Articles

Differentially methylated regions interrogated for metastable epialleles associate with offspring adiposity.

Aim: Assess if cord blood differentially methylated regions (DMRs) representing human metastable epialleles (MEs) associate with offspring adiposity in 588 maternal-infant dyads from the Colorado Health Start Study.Materials & methods: DNA methylation was assessed via the Illumina 450K array (~439,500 CpG sites). Offspring adiposity was obtained via air displacement plethysmography. Linear regression modeled the association of DMRs potentially representing MEs with adiposity.Results & conclusion: We identified two potential MEs, ZFP57, which associated with infant adiposity change and B4GALNT4, which associated with infancy and childhood adiposity change. Nine DMRs annotating to genes that annotated to MEs associated with change in offspring adiposity (false discovery rate<0.05). Methylation of approximately 80% of DMRs identified associated with decreased change in adiposity.

The Concentration of Liver-Expressed Antimicrobial Peptide 2 in Human Milk and Infant Plasma Is Positively Associated with Adiposity and Body Weight in the First Year of Life

BackgroundThe liver-expressed antimicrobial peptide 2 (LEAP2) is a recently recognized anorectic and glucose-regulating hormone with an unknown role in lactation. ObjectivesThe objectives of this study were as follows: 1) to assess LEAP2 presence in human milk and putative associations with infant body weight and adiposity in the first year of life, 2) to evaluate the impact of maternal weight status on LEAP2 concentration, and 3) to explore the relationship between infant plasma LEAP2 concentration and body weight and adiposity. MethodsThis prospective cohort observational study assessed LEAP2 concentration in plasma and milk from lactating women with normal weight (n = 26) or overweight or obesity (OW/OB, n = 26) at 6 mo postpartum and in 6-mo-old infant plasma, examining associations with metabolic and anthropometric variables at 6 mo and 1 y. Maternal plasma and milk leptin and insulin concentrations were also measured. LEAP2 expression in milk fat globules and single-cell-RNA-sequencing datasets was evaluated. ResultsLEAP2 was detected in all milk samples assessed (2.08 ± 0.65 ng/mL) and was positively associated with infant triceps (P = 0.022, Cohen f2 = 1.25) and subscapular (P = 0.008, f2 = 0.68) skinfolds at 1 y old. Maternal LEAP2 was positively associated with insulin (P = 0.005, f2 = 0.30) and prepregnancy body mass index (BMI) (P = 0.040, f2 = 0.17) and negatively associated with gestational weight gain (P = 0.008, f2 = 0.25) and postpartum weight retention (P = 0.036, f2 = 0.15). Maternal LEAP2 was higher in plasma (P = 0.039), but not milk of lactating women with OW/OB. Infant plasma LEAP2 (1.98 ± 0.28 ng/mL) was positively associated with weight (P = 0.004, f2 = 0.63), BMI (P = 0.049, f2 = 0.37), and weight-for-length (P = 0.024, f2 = 0.35) z-scores at 1 y old, predominantly in males. No evidence for LEAP2 mRNA expression was found in mammary cells. ConclusionsMilk LEAP2 is a bioactive component that plays a role in infant fat accretion in the first year of life. Although maternal LEAP2 responds to weight change in pregnancy and lactation, infant plasma LEAP2 might be involved in body weight regulation in early life.This trial was registered at clinicaltrials.gov as NCT05798676.

Nighttime eating during pregnancy and infant adiposity at 6 months of life.

Chrononutrition studies the relation between diet, circadian rhythms and metabolism, which may alter the metabolic intrauterine environment, influencing infant fat-mass (FM) development and possibly increasing obesity risk. To evaluate the association of chrononutrition in pregnancy and infant FM at 6 months. Healthy pregnant women and term-babies (n = 100pairs) from the OBESO cohort (2017-2023) were studied. Maternal registries included pregestational body-mass-index (BMI), gestational complications/medications, weight gain. Diet (three 24 h-recalls, 1 each trimester) and sleep-schedule (first and third trimesters) were evaluated computing fasting (hours from last-first meal), breakfast and dinner latencies (minutes between wake up-breakfast and dinner-sleep, respectively), number of main meals/day, meal skipping (≥1 main meal/d on three recalls) and nighttime eating (from 9:00 pm-5:59 am on three recalls). Neonatal weight, length, BMI/age were assessed. At 6 months, infant FM (kg, %; air-displacement plethysmography) was measured, and FM index (FMI-kgFM/length2) computed. Exclusive breastfeeding (EBF) was recorded. Multiple linear regression models evaluated the association between chrononutrition and 6 month infant FM. Mean fasting was 11.7 ± 1.3 h; breakfast, dinner latency were 87.3 ± 75.2, 99.6 ± 65.6 min, respectively. Average meals/day were 3.0 ± 0.5. Meal skipping was reported in 3% (n = 3) of women and nighttime eating in 35% (n = 35). Most neonates had normal BMI/age (88%, n = 88). Compared to those who did not, mothers engaged in nighttime-eating had infants with higher %FM (p = 0.019). Regression models (R 2 ≥ 0.308, p ≤ 0.001) showed that nighttime eating was positively associated with %FM (B: 2.7, 95%CI: 0.32-5.16). When analyzing women without complications/medications (n = 80), nighttime eating was associated with higher FM [%FM, B: 3.24 (95%CI: 0.59-5.88); kgFM, B: 0.20 (95%CI: 0.003-0.40); FMI, B: 0.54 (95%CI: 0.03-1.05)]. Infant sex and weight (6 months) were significant, while maternal obesity, pregnancy complications/medications, parity, energy intake, birth-BMI/age, and EBF were not. Maternal nighttime eating is associated with higher adiposity in 6 month infants.

Maternal exercise increases infant resting energy expenditure: preliminary results

Maternal obesity is associated with lower infant resting energy expenditure (REE), predisposing them to more rapid weight and adiposity gain through early infancy. Maternal exercise (ME) decreases infant adiposity and risk for childhood obesity; however, it remains unknown if this is in part mediated by changes in infant energy expenditure. Thus, we measured REE in 1-month-old infants from pregnant individuals who performed moderate-intensity exercise during pregnancy and compared it to infants from non-exercising controls. We observed higher oxygen respiratory rates (p = 0.003 for VO2 and p = 0.007 for VCO2) and REE (p = 0.002) in infants exposed to exercise in utero, independent of any differences in infant body composition. Furthermore, maternal BMI was significantly and inversely associated with infant REE in the control (r = −0.86, R2 = 0.74, p = 0.029), but not the exercise group (r = 0.33, R2 = 0.11, p = 0.473). Together, these findings associate ME with increasing infant energy expenditure which could be protective of subsequent infant adiposity gain. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146 and NCT04805502.

Maternal Exercise Improves Infant Mesenchymal Stem Cell Lipid Storage and Oxidation, and Decreases Infant Adiposity

Rates of pediatric obesity are continuously rising and are likely to translate into high incidence of metabolic disease later in life. Maternal exercise during pregnancy has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to a multitude of infant peripheral tissue (e.g., skeletal muscle) and remain involved in mature tissue repair and maintenance. Importantly, these cells preserve the phenotype of an offspring donor and represent a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC collected during a randomized controlled trial to investigate if maternal exercise, regardless of exercise mode, affects infant adiposity and fatty acid oxidation. Compared to control, we observed &gt;160% higher neutral lipid content in Ex-MSCs (p&lt;0.01). However, this finding was coupled with significantly higher complete fatty acid oxidation to CO2 and lower incomplete fat oxidation (ASM production) in Ex-MSCs (p≤0.05). Infants in the exercise group had significantly lower body fat percentage compared to same age infants of controls at one month of age (p≤0.05). There was no difference in lean body mass volume (p&gt;0.05) or infant one-month BMI (p=0.069). Together, these data indicate that maternal exercise exposure in utero is still associated with decreased infant adiposity one month after birth. MSC lipid content was positively associated with maternal fitness and exercise volume (p&lt;0.01) during pregnancy. Finally, an increase in average maternal exercise volume (MET*min/wk; r=-0.4, p≤0.05) and total gestational MET*min (r=-0.36, p≤0.05), but not VO2max (p=0.07) was associated with infant 1-month body fat percentage. Together, these data showcase the influence of maternal exercise exposure on improvements in cellular metabolism and at 1 month of age. Collectively, our data suggests that exposure to maternal exercise could contribute to lower adiposity in early infancy. This project was supported by the American Heart Association (18IPA34150006 to L.E.M.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of maternal exercise on infant mesenchymal stem cell mitochondrial function, insulin action, and body composition in infancy.

Maternal exercise (ME) has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. We found that infants from exercising mothers have improvements in MSC insulin signaling related to higher MSC respiration and fat oxidation, and expression and activation of energy-sensing and redox-sensitive proteins. Further, we found that infants exposed to exercise in utero were leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. These data suggest that infants from exercising mothers are relatively leaner, and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.

Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Does weight influence the course of RSV bronchiolitis in hospitalized infants?

Acute bronchiolitis is among the most common causes of hospitalizations in infants worldwide. Associations between weight and severity of respiratory syncytial virus (RSV) bronchiolitis remain unclear. The aim of this study was to evaluate this association. A single-center, retrospective cohort study of infants aged under 24 months, who were hospitalized between 2018 and 2022 for RSV bronchiolitis. Data from computerized medical records were extracted using the MDclone platform. Participants were divided into three groups according to weight percentiles: underweight (below 5th percentile), normal-weight, and overweight (above 85th percentile). A total of 1936 infants (mean age 6.3 months, 55% males) were included, comprising 274 infants who were underweight, 1470 with normal weight, and 192 with overweight. Underweight infants had a higher rate of admission to the pediatric intensive care unit (PICU) (9.1% vs. 3.5%, P < 0.005) and prolonged length of stay (LOS) in the hospital (3.13 vs. 2.79 days P < 0.001) compared to those with normal weight. Hyponatremia was also more common in the underweight group (23% vs. 15%, P < 0.001). A multivariable model accounting for prematurity and birthweight predicted a relative risk of 2.01 (95% CI 1.13-3.48, P = 0.015) for PICU admission and 1.42 (95% CI 1.17-1.7, P < 0.001) for a prolonged LOS. Being overweight was not associated with a more severe disease. Conclusion: Underweight infants, hospitalized for RSV bronchiolitis, had a more severe disease course with a higher complication rate, including PICU admission and prolonged LOS. Thus, careful attention and supervision should be given to this subgroup of infants. What is Known: • Established risk factors for severe bronchiolitis include prematurity, BPD, CHD, and compromised immunity. • Abnormal weight status has been associated with an increased risk for morbidity and mortality from infectious diseases, proposedly due to the effects on endocrine and immunologic systems. What is New: • Underweight infants hospitalized with RSV bronchiolitis face an independent risk of PICU admission and prolonged hospital stay. • Conversely, overweight infants did not display associations with severity measures in our study.

A Mediterranean diet plan in lactating women with obesity reduces maternal energy intake and modulates human milk composition - a feasibility study.

Maternal obesity is associated with increased concentrations of human milk (HM) obesogenic hormones, pro-inflammatory cytokines, and oligosaccharides (HMOs) that have been associated with infant growth and adiposity. The objective of this pilot study was to determine if adherence to a Mediterranean meal plan during lactation modulates macronutrients and bioactive molecules in human milk from mothers with obesity. Sixteen healthy, exclusively breastfeeding women with obesity (body mass index ≥30 kg/m2) enrolled between 4 and 5 months postpartum. The women followed a 4-week Mediterranean meal plan which was provided at no cost. Maternal and infant anthropometrics, HM composition, and infant intakes were measured at enrollment and at weeks 2 and 4 of the intervention. Thirteen mother-infant dyads completed the study. Additionally, participants from an adjacent, observational cohort who had obesity and who collected milk at 5 and 6 months postpartum were compared to this cohort. Participants' healthy eating index scores improved (+27 units, p < 0.001), fat mass index decreased (-4.7%, p < 0.001), and daily energy and fat intake were lower (-423.5 kcal/day, p < 0.001 and-32.7 g/day, p < 0.001, respectively) following the intervention. While HM macronutrient concentrations did not change, HM leptin, total human milk oligosaccharides (HMOs), HMO-bound fucose, Lacto-N-fucopentaose (LNFP)-II, LNFP-III, and difucosyllacto-N-tetrose (DFLNT) concentrations were lower following the intervention. Infant intakes of leptin, tumor necrosis factor (TNF)-α, total HMOs, HMO-bound fucose, LNFP-III and DFLNT were lower following the intervention. Specific components of the maternal diet (protein and fat) and specific measures of maternal diet quality (protein, dairy, greens and beans, fruit and vegetables) were associated with infant intakes and growth. Adherence to a Mediterranean meal plan increases dietary quality while reducing total fat and caloric intake. In effect, body composition in women with obesity improved, HM composition and infants' intakes were modulated. These findings provide, for the first time, evidence-based data that enhancing maternal dietary quality during lactation may promote both maternal and child health. Longer intervention studies examining the impact of maternal diet quality on HM composition, infant growth, and infant development are warranted.

The risk prediction of intergenerational transmission of overweight and obesity between mothers and infants during pregnancy.

Overweight and obesity in mothers before pregnancy lead to overweight and obesity in their offspring, which is the main form of intergenerational transmission of overweight and obesity in early life. Many factors, especially non-genetic factors, may influence intergenerational transmission, but little prediction research has been conducted. Therefore, we analyzed the status of intergenerational transmission in maternal and infant overweight and obesity. Second, we explored the factors during the pregnancy that might affect the the intergenerational transmission; According to the two application scenarios of pregnancy screen and self-management, risk prediction models for pregnant women were carried out. Based on a prospective birth cohort, a total of 908 mothers and offspring were followed up during early life. Follow-up visits were performed at the first trimester, second trimester, third trimester, delivery, 42 days after delivery, and 6 months and 12 months of age. The investigation methods included questionnaire survey, physical examination, biological sample collection and clinical data collection. In terms of risk prediction, univariate analysis was used to screen candidate predictors. Second, multivariable Cox proportional hazard regression models were used to determine the final selected predictors. Third, the corresponding histogram models were drawn, and then the 10-fold cross-validation methods were used for internal verification. Regarding intergenerational transmission of overweight and obesity between mothers and infants during pregnancy, the risk prediction model for pregnancy screen was constructed. The model established: h(t|X) = h0(t)exp.(- 0.95 × (Bachelor Degree or above) + 0.75 × (Fasting blood glucose in the second trimester) + 0.89 × (Blood pressure in the third trimester) + 0.80 × (Cholesterol in third trimester) + 0.55 × (Abdominal circumference in third trimester))., with good discrimination (AUC = 0.82) and calibration (Hosmer-Lemeshow2 = 4.17). The risk prediction model for self-management was constructed. The model established: h(t|X) = h0(t)exp. (0.98 × (Sedentary >18METs) + 0.88 × (Sleep index≥8) + 0.81 × (Unhealthy eating patterns Q3/Q4) + 0.90 × (Unhealthy eating patterns Q4/Q4) + 0.85 × (Depression)), with good discrimination (AUC = 0.75) and calibration (Hosmer-Lemeshow2 = 3.81). The risk predictions of intergenerational transmission of overweight and obesity between mothers and infants were performed for two populations and two application scenarios (pregnancy screening and home self-management). Further research needs to focus on infants and long-term risk prediction models.

Infant fat mass and later child and adolescent health outcomes: a systematic review

ObjectiveObesity and excess adiposity are leading causes of metabolic and cardiovascular morbidity and mortality. Early identification of individuals at risk is key for preventive strategies. We examined the relationship between...

The protective associations of breastfeeding with infant overweight and asthma are not dependent on maternal FUT2 secretor status.

Breastfeeding supplies infant gut bacteria with human milk oligosaccharides (HMOs) as a nutrient source. HMO profiles are influenced by the FUT2 gene, which encodes an enzyme affecting the fucosylation of milk sugars. 20 to 40% of individuals have a "non-secretor" polymorphism that inactivates the FUT2 gene, resulting in variable HMO proportions in milk. This has engendered a concerning, yet unfounded, perception that non-secretor milk is "inferior." To address this untested hypothesis, we re-analyzed two datasets in which we previously showed that breastfeeding was protective against early life asthma and excessive infant weight gain in the Canadian CHILD Cohort Study. Using stratified regression models, we found that the protective association of exclusive breastfeeding and infant asthma was not modified by maternal secretor status (secretors aOR: 0.53, 95% CI 0.31 to 0.92; non-secretors aOR: 0.36, 95% CI 0.12 to 1.04; p for interaction = 0.50, N = 2086 children). Similarly, the association of breastfeeding with lower infant BMI and weight gain velocity did not vary by maternal secretor status (infant BMI: secretors aβ -0.47, 95% CI -0.66 to -0.29; non-secretors aβ -0.46, 95% CI -0.78 to -0.13; p for interaction = 0.60; N = 1971 infants). Our results indicate that secretor and non-secretor mothers can equally promote infant growth and respiratory health through breastfeeding. These findings run contrary to the idea that non-secretor milk is an inferior food source, and instead reify the importance of breastfeeding for all infants. The results of this study can inform feeding recommendations that are applicable to all infants, regardless of maternal secretor status.

Anemia status of infants and young children aged six to thirty-six months in Ma'anshan City: A retrospective study.

Anemia in infants and young children can have long-term effects on cognitive and physical development. In Ma'anshan City, China, there has been growing concern about the prevalence of anemia among children aged 6 to 36 mo. Understanding the factors influencing this condition is crucial for targeted interventions and improving overall child health in the region. To analyze the anemia status and influencing factors of infants and young children aged 6 to 36 mo in Ma'anshan City, China. Providing scientific evidence for reducing the incidence of anemia and improving the health level of children in this age group. The study encompassed 37698 infants and young children, aged from 6 to 36 mo, who underwent health examinations at the Ma'anshan Maternal and Child Health Hospital from January 2018 to October 2022 were included in the study. Basic information, physical examination, and hemoglobin detection data were collected. Descriptive analysis was used to analyze the prevalence of anemia in children in the region, and univariate analysis was used to analyze the influencing factors of anemia. The mean hemoglobin level of infants and young children aged 9 to 36 mo increased with age, and the anemia detection rate decreased with age. The anemia detection rate in rural infants aged 6, 9, and 12 mo was higher than that in urban infants. Although the anemia detection rate was higher in 6-mo-old boys than girls, it was higher in 24-mo-old girls than boys. There were statistically significant differences in the anemia detection rates among 9-mo-old and 12-mo-old infants with different nutritional statuses (emaciation, overweight, obese, and normal). Moreover, there were no statistically significant differences in anemia detection rates among infants and young children with different nutritional statuses at other ages. Besides, the anemia detection rates in obese infants aged 9 and 12 mo were higher than those in normal and overweight infants, with statistically significant differences. Finally, there were no statistically significant differences in the anemia detection rates between emaciation infants and those with other nutritional statuses. The anemia situation among infants and young children aged 6 to 36 mo in Ma'anshan City, China, is relatively prominent and influenced by various factors. Our result shown that attention should be paid to the anemic infant and young child population, with strengthened education and targeted prevention and dietary guidance to help them establish good living habits, improve nutritional status, and reduce the occurrence of anemia to improve children's health levels.

Leptin receptor expression in blood mononuclear cells of lactating women is associated with infant body weight: Potential role as a molecular biomarker.

Molecular biomarkers of maternal leptin resistance associated with infant weight are needed. To evaluate gene expression of leptin receptor (LEPR), suppressor of cytokine signalling 3 (SOCS3) and insulin receptor in peripheral blood mononuclear cells (PBMCs) of lactating women and their relationship with infant body weight and adiposity. At day 10 postpartum, maternal gene expression in PBMCs as well as leptin and insulin concentrations in plasma and milk were assessed (n = 68). Infant weight and BMI z-scores, skinfolds and arm circumference were obtained at 10 days and/or at 3 months old. In mothers with pre-pregnancy overweight or obesity (OW/OB), LEPR expression was reduced (p = 0.013) whereas plasma and milk leptin and milk insulin concentrations were elevated. LEPR expression was positively related with infant weight z-score (Beta (95% CI): 0.40 (0.17, 0.63), p = 0.001) but not with leptin concentrations. SOCS3 expression was positively related with infant weight z-score (Beta (95% CI): 0.28 (0.04, 0.51), p = 0.024) and arm circumference (Beta (95% CI): 0.57 (0.32, 0.82), p < 0.001). Relationships remained significant after adjusting for maternal and infant confounders. LEPR and SOCS3 gene expression in PBMCs are novel maternal molecular biomarkers that reflect leptin resistance and are associated with infant body weight and adiposity.

Effect of prenatal micronutrient-fortified balanced energy-protein supplementation on maternal and newborn body composition: A sub-study from the MISAME-III randomized controlled efficacy trial in rural Burkina Faso.

Micronutrient-fortified balanced energy-protein (BEP) supplements are promising interventions to prevent intrauterine growth retardation in low- and middle-income countries. On the other hand, one concern with blanket prenatal supplementation programs using energy-dense supplements is that they could lead to more maternal and/or infant overweight. However, evidence is lacking on the potential effect of BEP on maternal and offspring body composition. This study evaluates the effects of micronutrient-fortified BEP supplementation during pregnancy on body composition of mothers and their newborns in rural Burkina Faso. The MISAME-III study is an open label individually randomized controlled trial where pregnant women (n = 1,897) of gestational age <21 weeks received either a combination of micronutrient-fortified BEP and iron-folic acid (IFA) tablets (i.e., intervention) or IFA alone (i.e., control). The prenatal phase of the MISAME-III study was conducted between the first enrollment in October 2019 and the last delivery in August 2021. In a sub-study nested under the MISAME-III trial, we evaluated anthropometry and body composition in newborns who were born starting from 17 November 2020 (n: control = 368 and intervention = 352) and their mothers (n: control = 185 and intervention = 186). Primary study outcomes were newborn and maternal fat-free mass (FFMI) and fat-mass (FMI) indices. We used the deuterium dilution method to determine FFMI and FMI and %FFM and %FM of total body weight within 1 month postpartum. Our main analysis followed a modified intention-to-treat approach by analyzing all subjects with body composition data available. Univariable and multivariable linear regression models were fitted to compare the intervention and control arms, with adjusted models included baseline maternal age, height, arm fat index, hemoglobin concentration and primiparity, household size, wealth and food security indices, and newborn age (days). At study enrollment, the mean ± SD maternal age was 24.8 ± 6.13 years and body mass index (BMI) was 22.1 ± 3.02 kg/m2 with 7.05% of the mothers were underweight and 11.5% were overweight. Prenatal micronutrient-fortified BEP supplementation resulted in a significantly higher FFMI in mothers (MD (mean difference): 0.45; 95% CI (confidence interval): 0.05, 0.84; P = 0.026) and newborns (MD: 0.28; 95% CI: 0.06, 0.50; P = 0.012), whereas no statistically significant effects were found on FMI. The effect of micronutrient-fortified BEP on maternal FFMI was greater among mothers from food secure households and among those with a better nutritional status (BMI ≥21.0 kg/m2 or mid-upper arm circumference (MUAC) ≥23 cm). Key limitations of the study are the relatively high degree of missing data (approximately 18%), the lack of baseline maternal body composition values, and the lack of follow-up body composition measurements to evaluate any long-term effects. Micronutrient-fortified BEP supplementation during pregnancy can increase maternal and newborn FFMI, without significant effects on FMI. ClinicalTrials.gov with identifier NCT03533712.

OR12-02-23 Offspring DNA Methylation of Metabolic Genes at Birth Associates With Maternal Folate and Choline Intake and Offspring Adiposity in Infancy and Childhood

OR12-02-23 Offspring DNA Methylation of Metabolic Genes at Birth Associates With Maternal Folate and Choline Intake and Offspring Adiposity in Infancy and Childhood

No strong evidence of the protein leverage hypothesis in pregnant women with obesity and their infants.

The goal of this study was to investigate the role of dietary protein on macronutrient and energy intake, maternal adiposity during pregnancy, and infant adiposity at birth. In 41 women with obesity, early-pregnancy (13-16 weeks) protein intake was assessed with food photography and expressed as a ratio of Estimated Average Requirements (EAR) in pregnancy for protein (0.88 g/kg/d), herein "protein balance." Energy intake was measured by the intake-balance method, gestational weight gain as grams per week, and fat mass by a three-compartment model. Spearman correlations and linear models were computed using R version 4.1.1 (p < 0.05 considered significant). Women had a mean (SD) age of 27.5 (4.8) years and a pregravid BMI of 34.4 (2.9), kg/m2 , and the majority were non-White (n = 23, 56.1%). Protein balance in early pregnancy was not significantly associated with energy intake across mid and mid/late pregnancy (β = 328.7, p = 0.30 and β = 286.2, p = 0.26, respectively) or gestational weight gain (β = 117.0, p = 0.41). Protein balance was inversely associated with fat mass in early, mid, and late pregnancy (β = -10.6, p = 0.01, β = -10.4, p = 0.03, β = -10.3, p = 0.03, respectively). Protein balance did not predict infant adiposity at birth (p > 0.05). Low protein intake may have been present before pregnancy, explaining early relationships with adiposity in this cohort. The protein leverage hypothesis is likely not implicated in the intergenerational transmission of obesity.

48-OR: Maternal Triglycerides in Diet-Controlled GDM Correlate with Newborn Triglycerides and Infant Fat Mass at Four Months of Life

The early hours of newborn (NB) life are critical for metabolic transition from the prenatal to postnatal period and possibly subsequent metabolic development. Although the relationship between maternal glucose and neonatal hypoglycemia in gestational diabetes (GDM) is strongly supported, little is known about the relationship between maternal and NB triglycerides (TG). We tested the hypothesis that maternal TG in GDM would correlate positively with NB pre-feed TG (NBpfTG) at 24hrs, and that NBpfTG would correlate with infant adiposity (Inf%fat). After GDM diagnosis (~28-30 wks), 16 diet-controlled GDM women (mean±SD; BMI 32±1) were randomized to eucaloric diets differing in carbohydrate and fat percentages (all food provided). Fasting (F) and 1-hr/2-hr postprandial (PP) glucose, insulin, and TG were measured during breakfast test meals at 31 and 36 wks. Newborn “fasting” blood (NBpfTG, NBpfGluc) was collected at 24 hrs. Inf%fat was measured at 24 hrs and 4 mos (PeaPod). All women met conventional glucose targets with diet alone; no neonates had hypoglycemia. At 31 but not 36 wks, maternal FTG and PPTG were correlated with NBpfTG (92±7mg/dL)(r=0.52-0.53, p=0.03 both) and NBpfTG correlated with 24 hr Inf%fat (r=0.50, p=0.06). Maternal fasting insulin, HOMA-IR, glucose and PP glucose at 31 and 36 wks correlated with Inf%fat at 24 hrs (r=0.47-0.68, p&amp;lt;0.05 all). Strikingly, NBpfTG were uniquely and highly correlated with Inf%fat at 4 mos (r=0.81, p&amp;lt;0.0001); NBpfGluc was not. Inf%fat was similar between maternal diet groups (p&amp;gt;0.05). These data show that maternal TG soon after GDM diagnosis correlated with NBpfTG, which in turn correlated with Inf%fat at 24 hrs, but had a sustained, stronger correlation with Inf%fat at 4 mos. This connection between 32 wk maternal TG and NBpfTG, and their association with Inf%fat from 24 hrs to 4 mos support future studies to address whether maternal TG might be therapeutically targeted to normalize fetal growth in well-controlled GDM. Disclosure P.J.Rozance: None. L.A.Barbour: None. E.Z.Dunn: None. S.S.Farabi: None. N.Hirsch: None. K.P.Rolloff: None. J.E.Friedman: None. T.L.Hernandez: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101659); Janssen Research and Development; National Center for Advancing Translational Sciences (UL1TR002535)

Maternal depressiveness and infant growth outcomes: Findings from the MAASTHI cohort study in India

ObjectiveThe study aims to examine the association between depressiveness in mothers on infant obesity and stunting at one year of age. MethodsWe enrolled 4829 pregnant women, followed them up at public health facilities in Bengaluru for one year after birth. We collected information on women's sociodemographic characteristics, obstetric history, depressive symptoms during pregnancy and delivery within 48 h. We took infant anthropometric measurements at birth and one year. We used chi-square tests, and calculated an unadjusted odds ratio using univariate logistic regression. We used multivariate logistic regression to examine the association between maternal depressiveness, childhood adiposity, and stunting. ResultsWe found that the prevalence of depressiveness was 31.8% in mothers who delivered in public health facilities in Bengaluru. Infants born to mothers with depressiveness at birth had 3.9 times higher odds of having larger waist circumference than infants born to mothers with no depressiveness (AOR: 3.96, 95% Confidence Interval: 1.24,12.58) and 1.9 times higher odds of having a larger sum of skinfold thickness (AOR: 1.99, 95% CI: 1.18,3.38). Additionally, we found that infants born to mothers with depressiveness at birth had 1.7 times higher odds of stunting than infants born to mothers with no depressiveness (AOR: 1.72; 95%CI: 1.22,2.43) after adjusting for confounders. ConclusionOur study highlights a high prevalence of depressiveness among mothers seeking antenatal care at a public hospital is associated with an increased risk of infant adiposity and stunting at one year. Further research is needed to understand the underlying mechanisms and identify effective interventions.

Circulating progranulin in human infants: relation to prenatal growth and early postnatal nutrition.

Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. We longitudinally assessed PGRN concentrations in infants born appropriate (AGA) or small for gestational age (SGA), the latter being at risk for obesity and type 2 diabetes, especially if they experience an excessive postnatal catch-up in weight and are formula-fed (FF). The study population consisted of 183 infants who were exclusively breast-fed [(BF), AGA, n = 66; SGA, n = 40], or FF (AGA, n = 31; SGA, n = 46) over the first 4 months. Assessments included auxology, fasting glucose, insulin, IGF-1, high-molecular-weight adiponectin, PGRN and body composition (by DXA), at birth, and at age 4 and 12 months. PGRN levels were low at birth and unaffected by prenatal growth. PGRN increased at 4 and 12 months, although to a lesser extent in SGA infants, and was unrelated to the mode of feeding. PGRN correlated with markers of adiposity, inflammation and insulin resistance in both AGA and SGA infants, especially in those FF. The attenuated increase of PGRN levels in SGA infants over the first year of life, along with the association to markers of unhealthy metabolic profile, might point to a role of PGRN in future disease risks. Progranulin (PGRN) displays pleiotropic biological functions and has been proposed as a biomarker for metabolic diseases. In healthy infants, PGRN concentrations are low at birth and experience a significant and progressive increase up to age 12 months, which is less marked in infants born small for gestational age (SGA) and is unrelated to the mode of feeding. Circulating PGRN is related to markers of adiposity, inflammation, and insulin sensitivity, especially in formula-fed SGA infants. PGRN may play a role in the metabolic adaptations of SGA infants during early life, potentially contributing to the risk for obesity and type 2 diabetes in this population.