Micronutrient, Metabolic, and Inflammatory Biomarkers through 24 Months of Age in Infants Receiving Formula with Added Bovine Milk Fat Globule Membrane through the First Year of Life: A Randomized Controlled Trial.

BACKGROUND: Bovine milk fat globule membrane (MFGM) added in infant formula supports typical growth and safety through 24 mo of age in term infants. OBJECTIVES: To assess micronutrient (zinc, iron, ferritin, transferrin receptor), metabolic [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin-like growth factor-1 (IGF-1), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory (leptin, adiponectin, high sensitivity C-reactive protein) secondary outcomes through 24 mo of age in infants who received standard cow's milk-based infant formula (SF), similar formula with added bovine MFGM (EF), or human milk (HM) through 1 y. METHODS: Infants whose parents agreed to a blood draw at baseline (<120 d of age) (SF = 80; EF = 80; HM = 83) were included. Subsequent collections (2-4 h fasting) occurred at D180, D365, and D730. Biomarker concentrations were analyzed and group changes tested using generalized estimating equations models. RESULTS: Only serum iron (+22.1 µg/dL) and HDL-C (+2.5 mg/dL) were significantly higher for EF compared with SF at D730. Prevalence of zinc deficiency for EF (-17.4%) and SF (-16.6%) at D180 and depleted iron stores for SF (+21.4%) at D180 and EF (-34.6%) and SF (-28.0%) at D365 were significantly different compared with HM. IGF-1 (ng/mL) for EF and SF was significantly higher at D180 (+8.9) and for EF (+8.8) at D365, and (+14.5) at D730 compared with HM. Insulin (µUI/mL) for EF (+2.5) and SF (+5.8) and HOMA-IR for EF (+0.5) and SF (+0.6) were significantly higher compared with HM at D180. TGs (mg/dL) for SF (+23.9) at D180, for EF (+19.0) and SF (+17.8) at D365, and EF (+17.3) and SF (+14.5) at D730 were significantly higher compared with HM. Zinc, ferritin, glucose, LDL-C and total cholesterol changes were higher in formula groups compared with HM between various time points. CONCLUSIONS: Micronutrient, metabolic, and inflammatory biomarkers were generally similar through 2 y in infants who received infant formula with or without added bovine MFGM. Over the 2 y, differences were observed between infant formulas and HM reference group. This trial was registered at clinicaltrials.gov as NTC02626143.

Growth of Very Low Birth Weight Infants Who Received a Liquid Human Milk Fortifier: A Randomized, Controlled Multicenter Trial.

OBJECTIVES: To evaluate growth (weight, length, head circumference, and knee-heel length [KHL]) in very low birth weight (VLBW) infants (500-1500 g) who received human milk with a liquid fortifier (LHMF) with high protein and fatty acid content versus a traditional powder fortifier (PHMF) for 45 days or until discharge. METHODS: This was a multicenter, randomized, controlled trial. An intention-to-treat analysis was performed to determine adverse events and withdrawal causes. We also performed an efficacy analysis involving the infants who completed at least 2 weeks of study. RESULTS: Of the 158 infants enrolled in the study, 146 completed at least 2 weeks, and 125 completed the entire study. The biodemographic characteristics were similar between groups, with no differences in increments of weight (22.9 vs 22.7 g kg-1 day-1), length (1.03 vs 1.09 cm/week), head circumference (0.91 vs 0.90 cm/week), or KHL (3.6 vs 3.3 mm/week). The KHL increment was greater in infants weighing >1 kg receiving LHMF (3.7 vs 3.2 mm/week, P = 0.027). Although there were no significant differences in serious adverse events, the incidence difference of the composite outcome death/necrotizing enterocolitis between groups warrants attention (1.3% with LHMF and 8.1% with PHMF). CONCLUSION: There were no differences in the overall growth between VLBW infants receiving either fortifier.

The effects of a combined intervention (docosahexaenoic acid supplementation and home-based dietary counseling) on metabolic control in obese and overweight pregnant women: the MIGHT study.

BACKGROUND: Lifestyle interventions have shown limited effectiveness in the prevention of gestational diabetes mellitus. The combination of lifestyle interventions with omega-3 polyunsaturated fatty acid supplementation could have a synergetic effect on maternal and offspring outcomes. OBJECTIVE: We evaluated the effects of docosahexaenoic acid supplementation among obese and overweight pregnant women (independently or combined with a dietary counseling intervention) on metabolic control in mothers and their offspring. STUDY DESIGN: This study was a randomized controlled trial with a 2×2 factorial design. The following inclusion criteria were used: <15 weeks of gestation; body mass index ≥25 kg/m2 at the first prenatal visit; singleton pregnancy; and 18 years of age or older. The recruited women (n=1002) were randomly allocated to 1 of the 4 parallel groups: Group 1: dietary counseling plus 800 mg/day of docosahexaenoic acid (n=250); Group 2: routine counseling plus 800 mg/day docosahexaenoic acid (n=252); Group 3: dietary counseling plus 200 mg/day docosahexaenoic acid (n=249); and Group 4: routine counseling plus 200 mg/day docosahexaenoic acid (n=251), considered as the reference group. The dietary intervention comprised 3 sessions, and it was focused on reducing the consumption of foods that most contributed to daily sugar intake. Primary outcomes were gestational diabetes mellitus defined according to the national guidelines; macrosomia (birthweight >4000 g); and neonatal insulin resistance (cord blood Homeostasis Model Assessment for Insulin Resistance ≥2.60), which was assessed in a subsample of 226 newborns. The analysis was by intention to treat and by efficacy. The trial was registered on ClinicalTrials.gov (NCT02574767). RESULTS: The overall incidence of gestational diabetes mellitus was 20.2% (Group 1, 21.0%; Group 2, 20.1%; Group 3, 18.9%; and Group 4, 20.9%). Mean birthweight was 3403.0 g (standard deviation, 575.3), and the incidence of macrosomia was 11.9% (Group 1, 13.2%; Group 2, 10.8%; Group 3, 11.5%; and Group 4, 12.1%). Median cord blood Homeostasis Model Assessment for Insulin Resistance was 0.9 (interquartile range, 0.6-1.7), and 10.2% showed cord blood insulin resistance (Group 1, 12.0%; Group 2, 12.0%; Group 3, 9.7%; and Group 4, 5.1%). No significant differences were found among groups regarding primary outcomes (P<.05). Glucose concentrations in the cord blood samples were lower in those adherents to the docosahexaenoic acid supplementation (P<.05). CONCLUSION: For women who were overweight or obese at the beginning of pregnancy, this combined intervention did not reduce the risk of gestational diabetes in mothers or macrosomia and insulin resistance in neonates.

Enteral Feeding and Necrotizing Enterocolitis: Does Time of First Feeds and Rate of Advancement Matter?

OBJECTIVE: The aim of the study was to determine if time to initial enteral feeding (EF) and rate of advancement are associated with necrotizing enterocolitis (NEC) or death. METHODS: Secondary analysis of prospectively collected data of very-low-birth-weight infants (VLBWI: 400--1500 g) born in 26 NEOCOSUR centers between 2000 and 2014. RESULTS: Among 12,387 VLBWI, 83.7% survived without NEC, 6.6% developed NEC and survived, and 9.6% had NEC and died or died without NEC (NEC/death). After risk adjustment, time to initial EF (median = 2 days) was not associated with NEC; however, delaying it was protective for NEC/death (odds ratio [OR] = 0.96; 95% confidence interval [CI] 0.93--0.99). A slower feeding advancement rate (FAR) was protective for NEC (OR = 0.97; 95% CI = 0.94-0.98) and for NEC/death (OR = 0.98; 95% CI = 0.96-0.99). CONCLUSIONS: In VLBWI, there was no association between an early initial EF and NEC, although delaying it was associated with less NEC/death. A slower FAR was associated with lower risk of both outcomes.

Maternal Obesity Is Associated With Higher Cord Blood Adipokines in Offspring Most Notably in Females.

BACKGROUND: Deleterious long-term effects in the offspring from women with pregravid obesity have been described; however, the evidence supporting early metabolic and inflammatory markers in the offspring at birth and gender differences are conflicting. OBJECTIVE: The present study aimed to compare cord blood adipokines and cytokines concentrations and anthropometric characteristics of the offspring of women with maternal obesity (MO) and normal-weight mothers (NWM). Also, maternal and neonatal variables on the association of maternal body mass index (BMI) with cord blood adipokines were evaluated. METHODS: A cross-sectional analysis of a subsample of mother-child dyads participating in a cohort study (n = 221) was assessed. Anthropometrics, cord blood adipokines (leptin and adiponectin) and cytokines (interleukin [IL]-1ß, IL-4, IL-10, IL-12 p40, IL-12p70, IL-13, and tumor necrosis factor α) concentrations in the offspring of normal-weight women (BMI >18.5 and <24.9 kg/m2) and women with pregravid obesity (BMI > 30 kg/m2) without comorbidities was performed. RESULTS: Offspring from mothers with obesity had higher birth weight, a higher proportion of large for gestational age, higher ponderal index, and heavier placentae than offspring from normal-weight mothers (P < 0.05). Within the offspring from women with obesity, males had significantly higher weight, length, the proportion of large-for-gestational-age newborns, higher weight for length ratio. Males had more efficient placentas than females (P < 0.05). Higher adiponectin and leptin in both sexes and higher leptin in female offspring of mothers with obesity after adjusting for birth size (P < 0.05) were found. Higher IL-12p40 in the offspring of women with MO with no other differences in other cytokines among groups were evidenced. CONCLUSIONS: Maternal obesity associates with a higher concentration of adiponectin and leptin in their offspring at birth. There is a relevant effect on anthropometrics in male offspring and on leptin in female newborn. Further studies need to evaluate the extension of these effects in postnatal life. TRAIL IDENTIFICATION NUMBER: NCT02903134.

Ultra-processed foods drive to unhealthy diets: evidence from Chile.

OBJECTIVES: To assess the consumption of ultra-processed foods and its association with the overall dietary content of nutrients related to non-communicable diseases (NCD) in the Chilean diet and to estimate the population attributable fraction of ultra-processed food consumption on the unhealthy nutrient content. DESIGN: Cross-sectional analysis of dietary data collected through a national survey (2010). SETTING: Chile. PARTICIPANTS: Chilean population aged ≥2 years (n 4920). RESULTS: In Chile, ultra-processed foods represented 28·6 % of the total energy intake. A significant positive association was found between the dietary share of ultra-processed foods and NCD-promoting nutrients such as dietary energy density (standardised regression coefficient (ß) = 0·22), content of free sugars (ß = 0·45), total fats (ß = 0·26), saturated fats (ß = 0·19), trans fats (ß = 0·09) and Na:K ratio (ß = 0·04), while a significant negative association was found with the content of NCD-protective nutrients such as K (ß = -0·19) and fibre (ß = -0·31). The content of Na (ß = 0·02) presented no significant association. Except for Na, the prevalence of inadequate intake of all nutrients (WHO recommendations) increased across quintiles of the dietary share of ultra-processed foods. With the reduction of ultra-processed foods consumption to the level seen among the 20 % lowest consumers (3·8 % (0-9·3 %) of the total energy from ultra-processed foods), the prevalence of nutrient inadequacy would be reduced in almost three-fourths for trans fats; in half for energy density (foods); in around one-third for saturated fats, energy density (beverages), free sugars and total fats; in near 20 % for fibre and Na:K ratio and in 13 % for K. CONCLUSIONS: In Chile, decreasing the consumption of ultra-processed foods is a potentially effective way to achieve the WHO nutrient goals for the prevention of diet-related NCD.

International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being.

Early Obesity: Risk Factor for Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), defined as fat accumulation greater than 5% in hepatocytes, may progress to fibrosis or cirrhosis later in life. NAFLD prevalence in adolescents has increased significantly in direct relation with obesity prevalence. Fatty liver has become the most frequent indication for liver transplantation in adults. OBJECTIVE: The aim of the study was to identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. METHODS: Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002 to 2003, with yearly anthropometric data collected over a 10-year period. The presence of intrahepatic fat in the livers of subjects 14 to 16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. RESULTS: 9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (≥7 kPa) had greater weight, BMI z-score, waist and hip circumference, and altered liver enzymes (P < 0.05). CONCLUSION: The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.

Effect of feeding mode on infant growth and cognitive function: study protocol of the Chilean infant Nutrition randomized controlled Trial (ChiNuT).

BACKGROUND: A central aim for pediatric nutrition is to develop infant formula compositionally closer to human milk. Milk fat globule membranes (MFGM) have shown to have functional components that are found in human milk, suggesting that addition of bovine sources of MFGM (bMFGM) to infant formula may promote beneficial outcomes potentially helping to narrow the gap between infants who receive human breast milk or infant formula. The objective of the current study is to determine how the addition of bMFGM in infant formula and consumption in early infancy affects physical growth and brain development when compared to infants fed with a standard formula and a reference group of infants fed with mother's own milk. METHODS: Single center, double-blind, and parallel randomized controlled trial. Planned participant enrollment includes: infants exclusively receiving breast milk (n = 200; human milk reference group; HM) and infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age (n = 340). The latter were randomized to receive one of two study formulas until 12 months of age: 1) cow's milk based infant formula that had docosahexaenoic (DHA) (17 mg/100 kcal) and arachidonic acid (ARA) (25 mg/100 kcal); 1.9 g protein/100 kcal; 1.2 mg Fe/100 kcal (Standard formula; SF) or 2) a similar infant formula with an added source of bovine MFGM (whey protein-lipid concentrate (Experimental formula; EF). Primary outcomes will be: 1) Physical growth (Body weight, length, and head circumference) at 730 days of age; and 2) Cognitive development (Auditory Event-Related Potential) at 730 days of age. Data will be analyzed for all participants allocated to each study feeding group. DISCUSSION: The results of this study will complement the knowledge regarding addition of bMFGM in infant formula including support of healthy growth and improvement of neurodevelopmental outcomes. TRIAL REGISTRATION: NCT02626143, registered on December 10th 2015.

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

BACKGROUND: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. METHODS: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. DISCUSSION: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. TRIAL REGISTRATION: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

Maternal exposure to intimate partner violence and breastfeeding practices in 51 low-income and middle-income countries: A population-based cross-sectional study.

BACKGROUND: Intimate partner violence (IPV) against women is a major global health issue, particularly in low- and middle-income countries (LMICs), that is associated with poor physical and mental health, but its association with breastfeeding practices is understudied. Both the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) recommend that children initiate breastfeeding within the first hour of birth and be exclusively breastfed for the first 6 months of life. Breastfeeding within the first hour of birth is critical to newborn survival, and exclusive breastfeeding for 6 months is recognised to offer significant health benefits to mothers and their infants. We examined the association of maternal exposure to IPV with early initiation of breastfeeding (within 1 hour of birth) and exclusive breastfeeding in the first 6 months. METHODS AND FINDINGS: We assessed population-based cross-sectional Demographic and Health Surveys (DHS) from 51 LMICs. Data from the most recent DHS in each country (conducted between January 2000 and January 2019) with data available on IPV and breastfeeding practices were used. By WHO region, 52.9% (27/51) were from Africa, 11.8% (6/51) from the Americas, 7.8% (4/51) from the Eastern Mediterranean, 11.8% (6/51) from Europe, 11.8% (6/51) from South-East Asia, and 3.9% (2/51) from the Western Pacific. We estimated multilevel logistic regression models for any IPV and each type of IPV separately (physical violence, sexual violence, and emotional violence), accounting for demographic and socioeconomic factors. Depending on specification, the sample size varied between 95,320 and 102,318 mother-infant dyads. The mean age of mothers was 27.5 years, and the prevalence of any lifetime exposure to IPV among mothers was 33.3% (27.6% for physical violence, 8.4% for sexual violence, and 16.4% for emotional violence). Mothers exposed to any IPV were less likely to initiate breastfeeding early (adjusted odds ratio [AOR]: 0.88 [95% CI 0.85-0.97], p < 0.001) and breastfeed exclusively in the first 6 months (AOR: 0.87 [95% CI 0.82-0.92], p < 0.001). The associations were similar for each type of IPV and were overall consistent across infant's sex and WHO regions. After simultaneously adjusting for all 3 types of IPV, all 3 types of IPV were independently associated with decreased likelihood of early breastfeeding initiation, but only exposure to physical violence was independently associated with a decreased likelihood of exclusively breastfeeding in the first 6 months. The main limitations of this study included the use of cross-sectional datasets, the possibility of residual confounding of the observed associations by household wealth, and the possibility of underreporting of IPV experiences attenuating the magnitude of observed associations. CONCLUSIONS: Our study indicates that mothers exposed to any form of IPV (physical, sexual, or emotional violence) were less likely to initiate breastfeeding early and breastfeed exclusively in the first 6 months. These findings may inform the argument for antenatal screening for IPV in LMICs and the provision of services to not only improve mothers' safety and well-being, but also support them in adopting recommended breastfeeding practices.

Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.

BACKGROUND: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. METHODS: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. RESULTS: LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. CONCLUSION: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.

Regional Overview on the Double Burden of Malnutrition and Examples of Program and Policy Responses: Latin America and the Caribbean.

BACKGROUND: Hunger, food insecurity, stunting, anemia, overweight, and noncommunicable diseases (NCDs) may coexist in the same person, household, and community in Latin America and the Caribbean (LAC). The double burden of malnutrition (DBM) is an important cause of disability and premature death, which could be addressed with comprehensive policies such as the Plan of Action for the Prevention of Obesity in Children and Adolescents. This paper summarizes the main policies and actions aimed to prevent undernutrition and obesity. SUMMARY: Several countries are implementing the Plan of Action, Caribbean Public Health Agency is actively supporting Ministries of Health, Education, and Sport to develop school nutrition policies and strategies to create health-promoting environments at school and in their surrounding communities. Chile is implementing the comprehensive child protection system "Chile Crece Contigo" that integrates health, social development, and educational activities to optimize growth and childhood cognitive-motor development. Brazil is implementing policies and plans to commit to international targets regarding food and nutrition security, NCDs and their risk factors. Key Messages: The DBM exists in the Americas and contributes to disability and premature death. The Region is making progress implementing policies and actions addressing the DBM. However, stronger political will and leadership are needed to enact legislation and policies that create and support enabling -environments.

Water, sanitation, and hygiene practices mediate the association between women's empowerment and child length-for-age z-scores in Nepal.

In Nepal, more than one-third of children are stunted. Prior studies have shown that women's empowerment in agriculture is associated with child (<2 years) length-for-age z-scores (LAZ) in Nepal. This study tests whether child dietary diversity (DD) and household water, sanitation, and hygiene (WASH) facilities and practices mediate the associations between women's empowerment and LAZ. With a cross-sectional dataset of 4,080 households from 240 rural communities across 16 districts of Nepal, we used ordinary least squares regression models to first estimate the associations between women's empowerment and LAZ for children 6 to 24 months (n = 1,402; our previous published analysis included all children <24 months of age), using the Women's Empowerment in Agriculture Index's Five Domains of Empowerment subindex. We used standardized structural equation models to test whether child DD and/or household WASH mediated the association between women's empowerment and child LAZ. Overall, women's empowerment was positively associated with child LAZ (ß = 0.24, P = 0.03), as found in our previous analyses. In the mediation analysis, women's empowerment was positively associated with WASH (ß = 0.78, P < 0.001), and in turn child LAZ (ß = 0.09, P < 0.001). Women's empowerment was not associated with DD, but DD was associated with LAZ (ß = 0.06, P = 0.05). Empowered women had better WASH practices than nonempowered women, which translated into higher child LAZ. Child DD was not a mediating factor in the association between women's empowerment and child LAZ. More research is needed to explore other pathways by which women's empowerment may affect child nutrition outcomes.

LGA-newborn from patients with pregestational obesity present reduced adiponectin-mediated vascular relaxation and endothelial dysfunction in fetoplacental arteries.

Maternal obesity is associated with large-for-gestational-age (LGA) neonates and programming of obesity-related cardiovascular disease in the offspring, however, the mechanisms that lead to the later are unclear. Presently, interpretations of NO-dependent changes in vascular function in LGA newborn from obese mothers are conflicting. Adiponectin improves endothelial function by increasing eNOS activity and NO production. We propose that LGAs from obese mothers present a diminished vascular response to adiponectin; thus, affecting eNOS and AMPK activation. Chorionic arteries, umbilical cord and primary cultures of umbilical artery endothelial cells (HUAEC) were collected at term (>38 weeks) from uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA) newborn. Vascular reactivity of chorionic plate arteries was assessed by wire myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK, phospho-AMPKαThr172 , eNOS, and phospho-eNOSSer1177 after stimulation with AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic artery relaxation in LGAs was diminished compared to control. In vitro studies showed no differences in expression of AdipoRs, total AMPK and, eNOS activation between groups; however, higher expression of total eNOS and AMPK activation in HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO production and eNOS activity compared to AGA in response to AdipoRon but no changes in AMPK activation. Placental endothelium of LGAs shows a diminished vascular response to adiponectin. Moreover, eNOS activation and adiponectin-dependent NO production is lower in HUAEC of LGA from obese mothers, indicating they present dysfuncional placental-endothelial responses.

Ultra-processed foods and added sugars in the Chilean diet (2010).

OBJECTIVE: To assess the consumption of ultra-processed foods and analyse its association with the content of added sugars in the Chilean diet. DESIGN: Cross-sectional study of national dietary data obtained through 24 h recalls and classified into food groups according to the extent and purpose of food processing (NOVA classification). SETTING: Chile. SUBJECTS: A probabilistic sample of 4920 individuals (aged 2 years or above) studied in 2010 by a national dietary survey (Encuesta Nacional de Consumo Alimentario). RESULTS: Ultra-processed foods represented 28·6 (se 0·5) % of total energy intake and 58·6 (se 0·9) % of added sugars intake. The mean percentage of energy from added sugars increased from 7·7 (se 0·3) to 19·7 (se 0·5) % across quintiles of the dietary share of ultra-processed foods. After adjusting for several potential sociodemographic confounders, a 5 percentage point increase in the dietary share of ultra-processed foods determined a 1 percentage point increase in the dietary content of added sugars. Individuals in the highest quintile were three times more likely (OR=2·9; 95 % CI 2·4, 3·4) to exceed the 10 % upper limit for added sugars recommended by the WHO compared with those in the lowest quintile, after adjusting for sociodemographic variables. This association was strongest among individuals aged 2-19 years (OR=3·9; 95 % CI 2·7, 5·9). CONCLUSIONS: In Chile, ultra-processed foods are important contributors to total energy intake and to the consumption of added sugars. Actions aimed at limiting consumption of ultra-processed foods are being implemented as effective ways to achieve WHO dietary recommendations to limit added sugars and processed foods, especially for children and adolescents.

[Position of the Latin American Society of Nutrition (SLAN) on the management of conflict of interest.] / Postura de la Sociedad Latinoamericana de Nutrición (SLAN) sobre el manejo de conflicto de intereses.

There is solid evidence documenting relationships between the food and beverage industry and academia that shows that industry sponsored research is likely to bias results in favor of industry. In Latin America, examples of these situations have been documented in Mexico, Brazil, Chile, Peru, Colombia, and Ecuador, among others. Due to the urgent need for studying and managing relationships between the food and beverage industry and the field of health and nutrition research, in 2017, the President of the Latin American Society of Nutrition (SLAN) appointed a Conflict of Interest Committee (CCI). The CCI was charged with the development of a proposal of a position for the management of conflict of interest (COI) for consideration by SLAN. This document details the work of CCI, and the position adopted by SLAN.

Existe evidencia sólida de la existencia de relaciones entre la industria de alimentos y bebidas y la academia. Ésta sugiere que la investigación patrocinada por la industria es susceptible de conferir sesgos a su favor en los resultados. En América Latina, se han documentado ejemplos de estas situaciones en México, Brasil, Chile, Perú, Colombia y Ecuador, por citar a algunos países. Ante la necesidad urgente de estudiar y gestionar las relaciones entre la industria de alimentos y bebidas y el campo de investigación en salud y nutrición, en 2017 el Presidente de la Sociedad Latinoamericana de Nutrición (SLAN) designó a un Comité de Conflicto de Intereses (CCI). El CCI tuvo la encomienda de hacer una propuesta de postura sobre manejo de conflicto de intereses (CDI) de la SLAN. El presente artículo refleja los trabajos del CCI y la postura que adoptó la SLAN.

N-Acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs.

KEY POINTS: Intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial epigenetic programming of the umbilical vessels. There is no evidence that this epigenetic programming is occurring on systemic fetal arteries. In IUGR guinea pigs we studied the functional and epigenetic programming of endothelial nitric oxide synthase (eNOS) (Nos3 gene) in umbilical and systemic fetal arteries, addressing the role of oxidative stress in this process by maternal treatment with N-acetylcysteine (NAC) during the second half of gestation. The present study suggests that IUGR endothelial cells have common molecular markers of programming in umbilical and systemic arteries. Notably, maternal treatment with NAC restores fetal growth by increasing placental efficiency and reverting the functional and epigenetic programming of eNOS in arterial endothelium in IUGR guinea pigs. ABSTRACT: In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetylcysteine (NAC) on fetal endothelial function and endothelial nitric oxide synthase (eNOS) programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, half of the sows receiving NAC in the drinking water (from day 34 until term). Fetal biometry and placental vascular resistance were followed by ultrasound throughout gestation. At term, umbilical arteries and fetal aortae were isolated to assess endothelial function by wire-myography. Primary cultures of endothelial cells (ECs) from fetal aorta, femoral and umbilical arteries were used to determine eNOS mRNA levels by quantitative PCR and analyse DNA methylation in the Nos3 promoter by pyrosequencing. Doppler ultrasound measurements showed that NAC reduced placental vascular resistance in IUGR (P < 0.05) and recovered fetal weight (P < 0.05), increasing fetal-to-placental ratio at term (∼40%) (P < 0.001). In IUGR, NAC treatment restored eNOS-dependent relaxation in aorta and umbilical arteries (P < 0.05), normalizing eNOS mRNA levels in EC fetal and umbilical arteries (P < 0.05). IUGR-derived ECs had a decreased DNA methylation (∼30%) at CpG -170 (from the transcription start site) and this epigenetic signature was absent in NAC-treated fetuses (P < 0.001). These data show that IUGR-ECs have common molecular markers of eNOS programming in umbilical and systemic arteries and this effect is prevented by maternal treatment with antioxidants.

IL-10 expression in macrophages from neonates born from obese mothers is suppressed by IL-4 and LPS/INFγ.

Obese women offspring have a higher risk of developing chronic diseases associated with an altered immune function. We aim to determine, in neonatal monocyte-derived macrophages, whether maternal obesity is associated with an altered expression and DNA methylation of pro- and anti-inflammatory genes, along with a higher pro-inflammatory response. Cord blood from newborns of obese (Ob) and lean (control) women were obtained at delivery. Monocytes were isolated and differentiated into macrophages, in which M1 (LPS/IFNγ) and M2 (IL-4) polarization were assayed. The mRNA levels for TNFα, IL-1ß, IL-12A, IL-12B, IL-10, and IL-4R were quantified by qPCR and the DNA methylation of candidate genes determined by pyrosequencing. RESULTS: Ob-monocytes had decreased levels of mRNA for pro-inflammatory cytokines IL-1ß, IL-10, and IL-12B compared with controls. Conversely, Ob-macrophages showed increased levels of mRNA for TNFα, IL-4R, and IL-10 compared with controls. M1 response was comparable between both groups, characterized by an important induction of TNFα and IL-1ß. In response to an M2 stimulus, control macrophages showed a decreased expression of inflammatory mediators while Ob-macrophages had an additional suppression of the anti-inflammatory mediator IL-10. Changes in IL-1ß (monocytes) and IL-10 (macrophages) in Ob-monocytes were paralleled by changes in their promoter DNA methylation in fetal monocytes. These results suggest that monocyte-derived macrophages from obese newborns show a basal anti-inflammatory phenotype with an unbalanced response to M1 and M2 polarization stimuli. The presence of changes in DNA methylation of key inflammatory genes in neonatal monocytes suggests an intrauterine programing of immune function by maternal obesity.

Determinants of volumetric breast density in Chilean premenopausal women.

PURPOSE: High mammographic breast density (BD) is a strong risk factor of breast cancer; however, little is known in women under 40 years of age. Recently, dual-energy X-ray Absorptiometry (DXA) has been developed as a low-dose method to measure BD in young populations. Thus, our aims were to describe BD in relation to risk factors in Chilean women under 40 years old and to explore the equivalence of DXA to mammography for the measurement of BD. METHODS: We selected 192 premenopausal Chilean female participants of the DERCAM study for whom we have anthropometric, sociodemographic, and gyneco-obstetric data. The subjects received both digital mammograms (Hologic) and breast DXA scans (GE iDXA). Mammographic BD was estimated using a fully automated commercial method (VOLPARA®) and BI-RADS. Breast DXA scans were performed using a standardized protocol and the % fibroglandular volume (%FGV) was estimated considering a two-compartment model of adipose and fibroglandular tissue. RESULTS: The mean age was 37 years (SD = 6.5) and 31.6% of the subjects were obese. The median %FGV and absolute FGV (AFGV) measured by DXA were 9% and 198.1 cm3 and for VOLPARA®, 8.6% and 58.0 cm3, respectively. The precision for %FGV after reposition was 2.8%. The correlation coefficients for %FGV, AFGV, and breast volume between DXA and mammography were over 0.7. Age and body mass index (BMI) were inversely associated with %FGV, and BMI was positively related to AFGV as estimated with DXA or mammography. We did not observe an association with gyneco-obstetric characteristics, education, and %FGV and AFGV; smoking was only associated with AFGV as measured by VOLPARA®. CONCLUSIONS: DXA is an alternative method to measure volumetric BD; thus, it could be used to continuously monitor BD in adult women in follow-up studies or to assess BD in young women.