Growth of late preterm infants fed nutrient-enriched formula to 120 days corrected age-A randomized controlled trial.

Objectives: We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age. Study design: A multi-center, randomized, controlled trial. Late preterm infants (34-37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA. Results: The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF (n = 22) and STF (n = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, -1.63 to 5.18, P = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16-0.85), P = 0.02]. Conclusion: We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size. Clinical Trial Registration: The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). "mailto:maria.makrides@sahmri.com" maria.makrides@sahmri.com.

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.

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.

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.

An ecological study of stillbirths in Mexico from 2000 to 2013.

OBJECTIVE: To examine trends in the rate of stillbirths at or after 21 weeks' gestation in Mexico from 2000 to 2013, identify factors associated with stillbirths and estimate subnational variability in stillbirth rates and the proportion of deaths occurring intrapartum. METHODS: This population-based, ecological study involved data from a national database on 263 475 stillbirths in 29 Mexican states and maternal sociodemographic factors. Subnational variability in the stillbirth rate in 2012 was investigated and stillbirths in 2013 were categorized as intrapartum or antepartum according to the fetus' skin condition. FINDINGS: The national stillbirth rate declined from 9.2 to 7.2 per 1000 births between 2000 and 2013 (i.e. -1.9% per year). The prevalence of stillbirths varied 3.9-fold between states. Stillbirths were associated, in particular, with: residence in Mexico City (odds ratio, OR: 1.71; 95% confidence interval, CI: 1.68-1.73) or central Mexico (OR: 1.36; 95% CI: 1.34-1.38); maternal education of 9 years or less (OR:1.10; 95% CI: 1.08-1.11) or 10 to 12 years (OR: 1.16; 95% CI: 1.14-1.18); mothers younger than 15 years (OR: 1.64; 95% CI: 1.55-1.72) or older than 34 years (OR: 1.68; 95% CI: 1.66-1.70); and male fetal sex (OR: 1.20; 95% CI: 1.19-1.21). Overall, 51% (7348/14 344) of fetal deaths occurred intrapartum. CONCLUSION: In Mexico, the total stillbirth rate declined between 2000 and 2013, however geographical variations were observed. Stillbirths were associated with sociodemographic factors. The proportion of intrapartum stillbirths was relatively high, suggesting that health system performance could be improved, especially at places of delivery.

Mortality from Congenital Heart Disease in Mexico: A Problem on the Rise.

BACKGROUND AND OBJECTIVES: Temporal trends in mortality from congenital heart disease (CHD) vary among regions. It is therefore necessary to study this problem in each country. In Mexico, congenital anomalies were responsible for 24% of infant mortality in 2013 and CHD represented 55% of total deaths from congenital anomalies among children under 1 year of age. The objectives of this study were to analyze the trends in infant mortality from CHD in Mexico (1998 to 2013), its specific causes, age at death and associated socio-demographic factors. METHODS: Population-based study which calculated the compounded annual growth rate of death rom CHD between 1998 and 2013. Specific causes, age at which death from CHD occurred and risk factors associated with mortality were analyzed for the year 2013. RESULTS: Infant mortality from CHD increased 24.8% from 1998 to 2013 (114.4 to 146.4/ 100,000 live births). A total of 3,593 CHD deaths occurred in 2013; the main causes were CHD with left-to-right shunt (n = 487; 19.8/100,000 live births) and cyanotic heart disease (n = 410; 16.7/100,000). A total of 1,049 (29.2%) deaths from CHD occurred during the first week of life. Risk factors associated with mortality from CHD were, in order of magnitude: non-institutional birth, rural area, birth in a public hospital and male sex. CONCLUSIONS: Mortality from CHD has increased in Mexico. The main causes were CHD with left-to-right shunt, which are not necessarily fatal if treated promptly. Populations vulnerable to death from CHD were identified. Approximately one-third of the CHD occurred during the first week of life. It is important to promote early diagnosis, especially for non-institutional births.

Meeting the challenge of providing neonatal nutritional care to very or extremely low birth weight infants in low-resource settings.

Most infant deaths (99%) occur in developing countries. The 14.9 million infants born prematurely (>11% of all live births) carry a particularly high mortality risk. This chapter discusses strategies to improve neonatal outcome under resource-restricted conditions, with a focus on nutritional interventions. Evidence-based interventions begin before conception with strategies to prevent and treat malnutrition among women of reproductive age, and micronutrient supplementation in pregnancy. As an example, a practically feasibly strategy of feeding very low birth weight infants in South Africa is presented. The use of parenteral nutrition can be limited by feasibility and affordability, but intravenous glucose and electrolytes should generally be provided after birth. Emphasis is put on the use of expressed own mother's milk without or with pasteurization from women without or with HIV infection, respectively, which is complemented by the use of pasteurized donor milk. If human milk fortifiers are not available, calcium and phosphate should be added, and high total daily feed volumes should be strived for, e.g. by frequent feedings. With restricted resources, human milk fortifiers or preterm formula can be used for high-risk groups such as infants with poor growth. Kangaroo mother care and breastfeeding should be actively encouraged.

Síndrome de Turner: Experiencia con un grupo selecto de población mexicana / Turner syndrome: experience with a select group from the Mexican population

Introducción. El síndrome de Turner (ST) es una condición genética que se presenta en mujeres por la ausencia parcial o total de un cromosoma X El objetivo de este documento es describir en un grupo selecto de pacientes con ST, la comorbilidad asociada a esta entidad, las dificultades del diagnóstico y algunos aspectos del entorno social de estas niñas. Métodos. Los datos analizados fueron obtenidos de integrantes de la Asociación de Síndrome de Turner de México A.C. Se realizó un cuestionario, mediciones antropométricas y pruebas de laboratorio para explorar comorbilidades, así como la problemática diagnóstica y social. Resultados. Se revelaron un diagnóstico tardío y un seguimiento inadecuado de las pacientes, que no permite la detección de comorbilidades, con menoscabo en la calidad de vida y falta de integración social de quienes nacen con este síndrome. Conclusiones. Es necesario fortalecer la educación continua de médicos de primer contacto y de la población general para realizar un diagnóstico temprano, y proveer un tratamiento oportuno y seguimiento de calidad a las personas con esta patología. De igual manera se requiere generar alianzas interinstitucionales y de las organizaciones gubernamentales con el propósito de disminuir dificultades sociales que se presentan en quienes padecen ST.

Background. Turner syndrome (TS) is a condition that presents in females with partial or total absence of the X chromosome. The aim of this article is to describe, in a select group of patients with Turner syndrome, comorbidity associated with this entity, diagnostic difficulties and some aspects related to the social environment of these patients. Analyzed data were obtained from members of the Turner Syndrome Association of Mexico AC. Methods. A questionnaire was administered and anthropometric measurements and laboratory studies were performed to explore comorbidities as well as diagnostic and social problems presented in these patients. Results. There was a delayed diagnosis and inadequate follow-up of these patients with poor detection of comorbidities and a probable lack of social integration of those females born with this syndrome. Conclusions. We need to continuously educate the medical community in regard to early detection and referral of these patients, both in the primary care setting as well as in the community, and also to implement strategies to improve social performance of those with Turner syndrome.

Vitamin D, vitamin A, maternal-perinatal considerations: old concepts, new insights, new questions.

Vitamins A and D are essential nutrients that play important roles in growth and development. Preterm and low birth weight infants have low levels of these nutrients and are at risk for developing detrimental health consequences associated with vitamin A and vitamin D deficiencies. Preliminary data suggest that vitamin A and D supplementation is needed to prevent deficiency. More work is needed to define optimal doses, timing, and modes of administration to ensure that an adequate supply of these vitamins is available to meet the critical needs during pregnancy and in high-risk neonates.

Intestinal mucosal defense system, Part 1. Consensus recommendations for immunonutrients.

When microbial communities colonize in the developing intestinal tract after birth, microorganisms interact with specific apical surface receptors on the enterocytes. This interaction triggers a response that prevents overexpression of inflammatory cytokines, thus providing protection from pathogen-induced mucosal damage. Multiple immune modulatory factors in human milk and innate humoral factors also control inflammatory responses, providing additional protective effects. Our understanding of the role of the luminal microbial communities or microbiota is growing rapidly as novel technologies provide new insights into their taxonomy, function during early development, and impact on life-long health. Multiple studies have evaluated the effects of the specific nutrients, glutamine, arginine, nucleotides, polyunsaturated fatty acids, and lactoferrin, on disease outcomes in premature infants. These studies support a role for nutrients to modulate host defense mechanisms in premature infants, to develop normal digestive function, to protect from bacterial translocation, and to preserve mucosal barrier integrity. These effects are clearly important. However, not enough is yet known to design specific clinical care practices that support a healthy microbiota.

Intestinal mucosal defense system, Part 2. Probiotics and prebiotics.

The interplay between microorganisms and the intestine of newborn infants is associated with diverse functional and clinical outcomes that result from the specific interactions among microbial communities, their products, and the unique characteristics of the gastrointestinal tract. Multiple mechanisms of action for infant formula ingredients with probiotic activity appear to exist. These mechanisms are thought to protect the host not only from intestinal diseases but also from systemic infection. However, questions about the safety of probiotics for preterm infants remain unanswered, particularly with regard to sepsis, immunomodulatory effects, and microbial resistance. Few well-designed studies have been conducted to evaluate the effects of probiotic, prebiotic, and synbiotic ingredients on relevant clinical outcomes in preterm infants. Although existing data are encouraging, there is insufficient evidence to recommend the routine use of these ingredients in all preterm infants.

Brote de bacteriemia nosocomial y colonización por Serratia marcescens en una Unidad de Cuidado Intensivo Neonatal / Nosocomial bacteremia and gastrointestinal tract colonization outbreak of Serratia marcescens in Neonatal Intensive Care Unit

Introducción. Se presenta la descripción de un brote de bacteriemia y colonización gastrointestinal nosocornial por Serratia marcescens en una Unidad de Cuidado Intensivo Neonatal (UCIN) de un hospital de tercer nivel. Material y métodos. El período epidémico fue considerado del 17 de mayo al 17 de junio de 2006. Se definió como caso a cualquier paciente con cultivo positivo para S. marcescens durante el período epidémico, ya que no se había identificado ningún cultivo positivo para esta bacteria en 6 meses de período pre-epidémico. Para identificar factores de riesgo de desarrollo de infección/colonización por S. mareescens, se compararon los casos con pacientes controles, definidos como aquéllos expuestos durante el período del brote sin aislamiento de esta bacteria. Todos los aislamientos de microorganismos fueron genotipificados por restricción con endonucleasa y electroforesis en gel por campos pulsados (PFGE). Resultados. Durante el período epidémico se identificaron 7 pacientes con cultivos positivos para S. marcescens y 12 controles. El paciente índice tuvo hemocultivo positivo y cuadro clínico de bacteriemia nosocomial, seguido por un caso de ventriculitis con cultivo positivo para S. marcescens en líquido cefalorraquídeo. Los otros 5 casos tuvieron aislamiento de S. marcescens en coprocultivos. Los cultivos de soluciones intravenosas y superficies inanimadas fueron negativos. El análisis univariado demostró que los pacientes con infección/colonización por S. marcescens tuvieron una estancia hospitalaria más prolongada (52 vs 27.9 días, P < 0.05), mayor frecuencia de alimentación enteral y presencia de sonda orogástrica al compararse con los controles. El patrón de PFGE fue idéntico en todos los aislamientos de S. mareescens. El reforzamiento de precauciones de contacto, incluyendo lavado de manos, además de cierre temporal de la UCIN, controló el problema de brote. Conclusión. El análisis epidemiológico complementado con técnicas de epidemiología molecular en este estudio aporta evidencia de un brote de 2 casos de bacteriemia nosocomial por transmisión cruzada de S. marcescens a través de un reservorio gastrointestinal. Estos hallazgos confirman la importancia que tienen las medidas de precauciones de contacto como el lavado de manos en el manejo de pacientes de la UCIN para prevenir infecciones nosocomiales y control de brotes.

Introduction. We investigated an outbreak of Serratia marcescens bloodstream infection (BSI)/colonization in patients from a Neonatal Intensive Care Unit (NICU) in a tertiary care pediatric Hospital. Material and methods. May 17 through June 17, 2006 was considered as the study period. A case was defined as any patient with S. marcescens-positive culture in the NICU during the outbreak period because no S. marcescens was identified in this area within 6 month of pre-epidemic period. To identify risk factors we compared patients with S. marcescens positive-cultures with controls exposed to the cases during the outbreak period without positive cultures. Genotyping of all S. marcescens isolates were evaluated by restriction endonuclease and pulsed-field gel electrophoresis (PFGE). Results. Seven S. marcescens positive cultures were identified; the index case had a positive blood culture with diagnosis of BSI, followed by a patient with CSF positive culture with diagnosis of ventriculitis and BSI. The remaining 5 cases had concurrent S. marcescens isolates from stool cultures (colonization). Environmental cultures (water, IV solutions and inanimate surfaces) were negative for these bacteria. According to univariate analysis, patients with S. marcescens stayed in the NICU longer than controls (52 vs 27.9 days, P < 0.05), they were more likely to have an orogastric tube in place and to receive enteral nutrition. All the S. marcescens had an identical pattern of PFGE analysis. Contact precaution, including hand washing, was reinforced in addition to temporary closing of the NICU in order to control the outbreak. Conclusions. This outbreak of S. marcescens was studied using epidemiological analysis and molecular biology techniques, confirming cross-transmission between cases associated to a possible gastrointestinal reservoir. Our findings underscore the importance of hand hygiene and other contact precaution methods in hospital settings, such as NICU.