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.

Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study.

BACKGROUND: Obesity predominantly affects populations in high-income countries and those countries facing epidemiological transition. The risk of childhood obesity is increased among infants who had overweight or obesity at birth, but in low-resource settings one in five infants are born small for gestational age. We aimed to study the relationships between: (1) maternal metabolite signatures; (2) fetal abdominal growth; and (3) postnatal growth, adiposity, and neurodevelopment. METHODS: In the prospective, multinational, observational INTERBIO-21st fetal study, conducted in maternity units in Pelotas (Brazil), Nairobi (Kenya), Karachi (Pakistan), Soweto (South Africa), Mae Sot (Thailand), and Oxford (UK), we enrolled women (≥18 years, with a BMI of less than 35 kg/m2, natural conception, and a singleton pregnancy) who initiated antenatal care before 14 weeks' gestation. Ultrasound scans were performed every 5±1 weeks until delivery to measure fetal growth and feto-placental blood flow, and we used finite mixture models to derive growth trajectories of abdominal circumference. The infants' health, growth, and development were monitored from birth to age 2 years. Early pregnancy maternal blood and umbilical cord venous blood samples were collected for untargeted metabolomic analysis. FINDINGS: From Feb 8, 2012, to Nov 30, 2019, we enrolled 3598 pregnant women and followed up their infants to 2 years of age. We identified four ultrasound-derived trajectories of fetal abdominal circumference growth that accelerated or decelerated within a crucial 20-25 week gestational age window: faltering growth, early accelerating growth, late accelerating growth, and median growth tracking. These distinct phenotypes had matching feto-placental blood flow patterns throughout pregnancy, and different growth, adiposity, vision, and neurodevelopment outcomes in early childhood. There were 709 maternal metabolites with positive effect for the faltering growth phenotype and 54 for the early accelerating growth phenotype; 31 maternal metabolites had a negative effect for the faltering growth phenotype and 76 for the early accelerating growth phenotype. Metabolites associated with the faltering growth phenotype had statistically significant odds ratios close to 1·5 (ie, suggesting upregulation of metabolic pathways of impaired fetal growth). The metabolites had a reciprocal relationship with the early accelerating growth phenotype, with statistically significant odds ratios close to 0.6 (ie, suggesting downregulation of fetal growth acceleration). The maternal metabolite signatures included 5-hydroxy-eicosatetraenoic acid, and 11 phosphatidylcholines linked to oxylipin or saturated fatty acid sidechains. The fungicide, chlorothalonil, was highly abundant in the early accelerating growth phenotype group. INTERPRETATION: Early pregnancy lipid biology associated with fetal abdominal growth trajectories is an indicator of patterns of growth, adiposity, vision, and neurodevelopment up to the age of 2 years. Our findings could contribute to the earlier identification of infants at risk of obesity. FUNDING: Bill & Melinda Gates Foundation.

Added bovine milk fat globule membrane in formula: Growth, body composition, and safety through age 2: An RCT.

OBJECTIVE: The aim of this study was to assess the effects of an experimental formula (EF) with added whey protein-lipid concentrate (5 g/L; source of bovine milk fat globule membrane [bMFGM]) on growth, body composition, and safety through 24 mo of age in term infants. METHODS: This was a double-blinded, randomized controlled trial conducted in Santiago, Chile. Infants were enrolled before 120 d and randomized to receive standard cow's milk-based formula (SF) or EF through the first year of life. Breastfed infants were the reference (HM). Growth (weight-for-age [WAZ], length-for-age [LAZ], BMI-for-age [BAZ], headcircumference-for-age [HCZ] z-scores); body composition (fat mass [FM] and fat-free mass, percentage body fat [%BF]); and adverse events through day 730 were recorded. Outcome trajectories were analyzed using a single generalized estimating equation testing the interaction between group and visit. RESULTS: We recruited 582 infants (HM = 235; SF = 174; EF = 173); 478 (>80%) completed the study. At baseline, only WAZ was different between the formula groups (0.14 lower in EF versus SF group, P = 0.035). WAZ, LAZ, and BAZ trajectories were higher from baseline to days 365 and 730 in EF or SF compared with HM (all P < 0.05). No differences in changes in body composition were observed between the formula groups. For EF versus HM, %BF was lower at day 180; however, this difference reversed from day 365. Fat-free mass was higher in formula groups compared with HM at all time points. No group difference in adverse event incidence rate was detected. CONCLUSION: During the first 2 y of life, infant formula with added bMFGM supports typical growth and safety compared with a standard formula.

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.

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.

Fetal cranial growth trajectories are associated with growth and neurodevelopment at 2 years of age: INTERBIO-21st Fetal Study.

Many observational studies and some randomized trials demonstrate how fetal growth can be influenced by environmental insults (for example, maternal infections)1 and preventive interventions (for example, multiple-micronutrient supplementation)2 that can have a long-lasting effect on health, growth, neurodevelopment and even educational attainment and income in adulthood3. In a cohort of pregnant women (n = 3,598), followed-up between 2012 and 2019 at six sites worldwide4, we studied the associations between ultrasound-derived fetal cranial growth trajectories, measured longitudinally from <14 weeks' gestation, against international standards5,6, and growth and neurodevelopment up to 2 years of age7,8. We identified five trajectories associated with specific neurodevelopmental, behavioral, visual and growth outcomes, independent of fetal abdominal growth, postnatal morbidity and anthropometric measures at birth and age 2. The trajectories, which changed within a 20-25-week gestational age window, were associated with brain development at 2 years of age according to a mirror (positive/negative) pattern, mostly focused on maturation of cognitive, language and visual skills. Further research should explore the potential for preventive interventions in pregnancy to improve infant neurodevelopmental outcomes before the critical window of opportunity that precedes the divergence of growth at 20-25 weeks' gestation.

Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years: Results From the INTERBIO-21st Newborn Study.

Importance: The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures. Objective: To examine the association between specific preterm-birth phenotypes and clinical, growth, and neurodevelopmental differences among preterm newborns compared with term newborns up to age 2 years. Design, Setting, and Participants: The INTERBIO-21st study included a cohort of preterm and term newborn singletons enrolled between March 2012 and June 2018 from maternity hospitals in 6 countries worldwide who were followed up from birth to age 2 years. All pregnancies were dated by ultrasonography. Data were analyzed from November 2019 to October 2020. Exposures/Interventions: Preterm-birth phenotypes. Main Outcomes and Measures: Infant size, health, nutrition, and World Health Organization motor development milestones assessed at ages 1 and 2 years; neurodevelopment evaluated at age 2 years using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) tool. Results: A total of 6529 infants (3312 boys [50.7%]) were included in the analysis. Of those, 1381 were preterm births (mean [SD] gestational age at birth, 34.4 [0.1] weeks; 5148 were term births (mean [SD] gestational age at birth, 39.4 [0] weeks). Among 1381 preterm newborns, 8 phenotypes were identified: no main maternal, fetal, or placental condition detected (485 infants [35.1%]); infections (289 infants [20.9%]); preeclampsia (162 infants [11.7%]); fetal distress (131 infants [9.5%]); intrauterine growth restriction (110 infants [8.0%]); severe maternal disease (85 infants [6.2%]); bleeding (71 infants [5.1%]); and congenital anomaly (48 infants [3.5%]). For all phenotypes, a previous preterm birth was a risk factor for recurrence. Each phenotype displayed differences in neonatal morbidity and infant outcomes. For example, infants with the no main condition detected phenotype had low neonatal morbidity but increased morbidity and hospitalization incidence at age 1 year (odds ratio [OR], 2.2; 95% CI, 1.8-2.7). Compared with term newborns, the highest risk of scoring lower than the 10th centile of INTER-NDA normative values was observed in the fine motor development domain among newborns with the fetal distress (OR, 10.6; 95% CI, 5.1-22.2) phenotype. Conclusions and Relevance: Results of this study suggest that phenotypic classification may provide a better understanding of the etiologic factors and mechanisms associated with preterm birth than continuing to consider it an exclusively time-based entity.

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.

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.

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.

Maternal obesity is associated with a sex-specific epigenetic programming in human neonatal monocytes.

Aim: To determine changes in global DNA methylation in monocytes from neonates of women with obesity, as markers of an immune programming resulting from maternal obesity. Materials & methods: Cord blood monocytes were obtained from neonates born to women with obesity and normal weight, genome-wide differentially methylated CpGs were determined using an Infinium MethylationEPIC-BeadChip (850K). Results: No clustering of samples according to maternal BMI was observed, but sex-specific analysis revealed 71,728 differentially methylated CpGs in female neonates from women with obesity (p < 0.01). DAVID analysis showed increased methylation levels within genes involved in the innate immune response and inflammation. Conclusion: Maternal obesity induces, in a sex-specific manner, an epigenetic programming of monocytes that could contribute to disease later in life. Clinical trial registry: This study is registered in ClinicalTrials.gov NCT02903134.

Periodic Revisions of the International Choices Criteria: Process and Results.

Unhealthy diets contribute to an increased risk of non-communicable diseases, which are the leading causes of deaths worldwide. Nutrition policies such as front-of-pack labeling have been developed and implemented globally in different countries to stimulate healthier diets. The Choices Programme, including the International Choices criteria, is an established tool to support the implementation of such policies. The Choices criteria were developed to define the healthier choices per product group, taking saturated fatty acids, trans fatty acids, sodium, sugars, energy, and fiber into account. To keep these criteria updated, they are periodically revised by an independent international scientific committee. This paper explains the most important changes resulting from revisions between 2010 and 2016 and describes the process of the latest revision, resulting in the International Choices criteria version 2019. Revisions were based on national and international nutrition and dietary recommendations, large food composition databases, and stakeholders' feedback. Other nutrient profiling systems served as benchmarks. The product group classification was adapted and new criteria were determined in order to enhance global applicability and form a credible, intuitively logical system for users. These newly developed criteria will serve as an international standard for healthier products and provide a guiding framework for food and nutrition policies.

Leptin in Cord Blood Associates with Asthma Risk at Age 3 in the Offspring of Women with Gestational Obesity.

Rationale: Maternal obesity is associated with asthma in the offspring. Whether cord blood leptin is associated with risk of asthma in offspring is unclear.Objectives: To assess whether cord blood leptin from women with pregestational obesity predict preschool asthma.Methods: In this birth cohort study, we divided pregnant women into three weight categories during the first obstetric visit: normal (NL), overweight (OW), and obese (OB).Results: We followed the offspring recording atopy, wheezing, and other respiratory illnesses through 30 months of age. Cord blood and peripheral blood at 30 months of age were taken to measure cytokines, adipokines, metabolic biomarkers, and specific immunoglobulin E. Adjusted regression models were used to evaluate the association between maternal obesity and offspring asthma risk, defined by a positive Asthma Predictive Index. Three hundred thirty-nine mothers were recruited; 140 offspring were born from NL, 80 from OW, and 119 from OB mothers. OB women were older and less educated and had higher parity and higher C-section frequency. Offspring from OB women had higher birthweight, head circumference, and placental weight compared with other groups. The proportion of Asthma Predictive Index positive at 30 months of age was 12.2% in the NL, 14.7% in the OW, and 16.8% in the OB group (P = 0.18). Offspring from OB women had higher leptin, leptin/adiponectin ratio, interleukin-10, and insulin than the OW group and higher leptin than the NL group. In the adjusted analysis, offspring from OB mothers with high cord blood leptin had increased risk of asthma (adjusted odds ratio, 1.30; 95% confidence interval, 1.1-1.55; P = 0.003).Conclusions: Offspring from obese mothers with high cord blood leptin have 30% higher asthma risk at age 3.Clinical trial registered with ClinicalTrials.gov (NCT02903134).

Effectiveness of a normative nutrition intervention in Chilean pregnant women on maternal and neonatal outcomes: the CHiMINCs study.

BACKGROUND: Some nutritional interventions have shown their efficacy in reducing gestational weight gain (GWG); however, their applicability in routine care is limited. OBJECTIVE: We assessed the effectiveness of a low-intensity and high-coverage nutritional intervention on maternal and offspring outcomes; the intervention enhanced existing nutritional health care standards and practices at the primary health care level in Chile. METHODS: This study was a cluster-randomized controlled trial of 12 primary health care centers (PHCCs) from Santiago, Chile. PHCCs were randomly allocated to either nutritional intervention [intervention group (IG), n = 5] or routine care [control group (CG), n = 7]. A total of 4631 pregnant women were recruited (IG, n = 2565; and CG, n = 2066). Primary outcomes were adequate GWG and glycemic control in mothers and birth weight, birth length, macrosomia, and large for gestational age in neonates. The intervention consisted of 4 key actions: training of health care professionals on nutritional recommendations, counseling of pregnant women on diet and physical activity recommendations, offering a physical activity program implemented in the participating PHCCs, and adequate referral to dietitians. Women randomly assigned to the CG received routine antenatal care. RESULTS: At baseline, the mean age was 26.1 y; 45% of women were primipara and 24% were obese. No differences were found in the percentage of women achieving adequate GWG (IG: 30.3%, compared with CG: 31.3%; OR: 0.94; 95% CI: 0.81, 1.09), but women in the IG had lower GWG than those in the CG (11.3 compared with 11.9 kg; mean difference: -0.63 kg; 95% CI: -1.19, -0.08). Effects of the intervention were significantly higher in women with obesity at the begining of pregnancy (mean difference: -1.24 kg; 95% CI: -2.18, -0.30; P for interaction < 0.05). No differences were found between groups regarding maternal glycemic control or neonatal outcomes. CONCLUSIONS: Our findings demonstrate that a low-intensity, high-coverage intervention delivered through the Chilean public health care system under standard operating conditions reduces GWG and has the potential for successful scale-up. This trial was registered at clinicaltrials.gov as NCT01916603.

Predictive anthropometric models of total and truncal body fat in Chilean children.

OBJECTIVES: This study aimed to develop predictive anthropometric models for total and truncal body fat in Chilean children using the following anthropometric measurements: weight, height, skinfold thickness, and circumference. METHODS: This cross-sectional study included 669 Chilean children (12.0 y ± 1.3) in Tanner stage IV from the Growth and Obesity Chilean Cohort Study. Anthropometric measurements and dual-energy X-ray absorptiometry were determined to calculate total and truncal body fat. Prediction models were fitted by linear regression analysis. RESULTS: The predictive equation for log total body fat (kg) was 0.449 + 0.049 (body mass index in kg/m2) + 0.018 (triceps skinfold in mm) + 0.012 (biceps skinfold in mm) + 0.019 (brachial circumference in cm) + 0.091 (sex: 1 = boy, 2 = girl) + 0.018 (age in y). The predictive equation for log truncal fat (kg) was -2.107 + 0.046 (waist circumference in cm) + 0.010 (subscapular skinfold in mm) + 0.259 (sex: 1 = boy, 2 = girl) + 0.006 (age in y). The test of concordance between the predictive equations of total and truncal body fat with gold standard was r = 0.85 and 0.91, respectively. CONCLUSIONS: In Chilean children, the high correlation between observed and predicted values enabled us to develop predictive equations for total and truncal body fat for children.

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.

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.

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.