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1.
Cell Mol Biol Lett ; 29(1): 29, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38431560

RESUMEN

Malignant melanoma remains the most lethal form of skin cancer, exhibiting poor prognosis after forming distant metastasis. Owing to their potential tumor-suppressive properties by regulating oncogenes and tumor suppressor genes, microRNAs are important player in melanoma development and progression. We defined the loss of miR-101-3p expression in melanoma cells compared with melanocytes and melanoblast-related cells as an early event in tumor development and aimed to understand the tumor suppressive role of miR-101-3p and its regulation of important cellular processes. Reexpression of miR-101-3p resulted in inhibition of proliferation, increase in DNA damage, and induction of apoptosis. We further determined the nuclear structure protein Lamin B1, which influences nuclear processes and heterochromatin structure, ATRX, CASP3, and PARP as an important direct target of miR-101-3p. RNA sequencing and differential gene expression analysis after miR-101-3p reexpression supported our findings and the importance of loss of mir-101-3p for melanoma progression. The validated functional effects are related to genomic instability, as recent studies suggest miRNAs plays a key role in mediating this cellular process. Therefore, we concluded that miR-101-3p reexpression increases the genomic instability, leading to irreversible DNA damage, which leads to apoptosis induction. Our findings suggest that the loss of miR-101-3p in melanoma serves as an early event in melanoma progression by influencing the genomic integrity to maintain the increased bioenergetic demand.


Asunto(s)
Melanoma , MicroARNs , Neoplasias Cutáneas , Humanos , Melanoma/genética , MicroARNs/metabolismo , Neoplasias Cutáneas/genética , Apoptosis/genética , Genómica , Inestabilidad Genómica , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica
2.
Am J Perinatol ; 2023 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-37494586

RESUMEN

OBJECTIVE: This study aimed to determine whether clinically integrated Breastfeeding Peer Counseling (ci-BPC) added to usual lactation care reduces disparities in breastfeeding intensity and duration for Black and Hispanic/Latine participants. STUDY DESIGN: This study is a pragmatic, randomized control trial (RCT) of ci-BPC care at two ci-BPC-naïve obstetrical hospital facilities in the greater Chicago area. Participants will include 720 patients delivering at Hospital Site 1 and Hospital Site 2 who will be recruited from eight prenatal care sites during midpregnancy. Participants must be English or Spanish speaking, planning to parent their child, and have no exposure to ci-BPC care prior to enrollment. Randomization will be stratified by race and ethnicity to create three analytic groups: Black, Hispanic/Latine, and other races. RESULTS: The primary outcome will be breastfeeding duration. Additional outcomes will include the proportion of breastmilk feeds during the delivery admission, at 6-week postdelivery, and at 6-month postdelivery. A process evaluation will be conducted to understand implementation outcomes, facilitators, and barriers to inform replication and scaling of the innovative ci-BPC model. CONCLUSION: This research will produce findings of relevance to perinatal patients and their families, the vast majority of whom desire to provide breastmilk to their infants and require support to succeed with their feeding goals. As the largest RCT of ci-BPC in the United States to date, this research will improve the quality of evidence available regarding the effectiveness of ci-BPC at reducing disparities. These findings will help patients and stakeholders determine the benefits of accepting and adopting the program and inform policies focused on improving perinatal care and reducing maternal/child health disparities. This study is registered with Clinical Trial (identifier: NCT05441709). KEY POINTS: · Ci-BPC can promote racial breastfeeding equity.. · Ci-BPC has not been tested as a generalized lactation strategy in prior trials and is underused.. · This RCT will identify if ci-BPC can reduce breastfeeding disparities for Black and Hispanic patients..

3.
BMC Pediatr ; 22(1): 27, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34996401

RESUMEN

BACKGROUND: Black very low birth weight (VLBW; < 1500 g birth weight) and very preterm (VP, < 32 weeks gestational age, inclusive of extremely preterm, < 28 weeks gestational age) infants are significantly less likely than other VLBW and VP infants to receive mother's own milk (MOM) through to discharge from the neonatal intensive care unit (NICU). The costs associated with adhering to pumping maternal breast milk are borne by mothers and contribute to this disparity. This randomized controlled trial tests the effectiveness and cost-effectiveness of an intervention to offset maternal costs associated with pumping. METHODS: This randomized control trial will enroll 284 mothers and their VP infants to test an intervention (NICU acquires MOM) developed to facilitate maternal adherence to breast pump use by offsetting maternal costs that serve as barriers to sustaining MOM feedings and the receipt of MOM at NICU discharge. Compared to current standard of care (mother provides MOM), the intervention bundle includes three components: a) free hospital-grade electric breast pump, b) pickup of MOM, and c) payment for opportunity costs. The primary outcome is infant receipt of MOM at the time of NICU discharge, and secondary outcomes include infant receipt of any MOM during the NICU hospitalization, duration of MOM feedings (days), and cumulative dose of MOM feedings (total mL/kg of MOM) received by the infant during the NICU hospitalization; maternal duration of MOM pumping (days) and volume of MOM pumped (mLs); and total cost of NICU care. Additionally, we will compare the cost of the NICU acquiring MOM versus NICU acquiring donor human milk if MOM is not available and the cost-effectiveness of the intervention (NICU acquires MOM) versus standard of care (mother provides MOM). DISCUSSION: This trial will determine the effectiveness of an economic intervention that transfers the costs of feeding VLBWand VP infants from mothers to the NICU to address the disparity in the receipt of MOM feedings at NICU discharge by Black infants. The cost-effectiveness analysis will provide data that inform the adoption and scalability of this intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04540575 , registered September 7, 2020.


Asunto(s)
Leche Humana , Madres , Lactancia Materna/métodos , Femenino , Humanos , Lactante , Recién Nacido , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Ensayos Clínicos Controlados Aleatorios como Asunto
4.
Am J Perinatol ; 39(12): 1348-1353, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-33406537

RESUMEN

OBJECTIVE: This study was aimed to evaluate the impact of donor milk (DM) received in the first 28 days of life (DOL) on neurodevelopmental (ND) outcome at 20-months corrected age (CA) in very low birth weight (VLBW) infants. STUDY DESIGN: A total of 84 infants born in 2011 to 2012 who received only mother's own milk (MOM) and/or preterm formula (PF) was compared with 69 infants born in 2013 to 2014 who received MOM and/or DM. Daily enteral intake of MOM, DM, and PF was collected through 28 DOL. ND outcomes were assessed with the Bayley-III. Multiple regression analyses adjusted for the effect of social and neonatal risk factors alongside era of birth on ND outcome. RESULTS: Infants exposed to DM were born to older mothers (p < 0.01) and had higher incidence of severe brain injury (p = 0.013). Although DM group infants received first feed at earlier DOL (p < 0.001), there were no differences in MOM intake at DOL 14 or 28 between the two groups. In regression analyses, DM group did not predict 20-month ND outcome. CONCLUSION: There were no differences in ND outcome between infants born before and after the introduction of DM. This may have been due to the similar percent of MOM at DOL 14 and 28 in the two eras. KEY POINTS: · Donor milk use is increasing in VLBW infant. The impact of donor milk on neurodevelopment is unclear.. · Provision of mother's own milk was high at days of life 14 and 28 for both groups of infants.. · Donor milk was not associated with improved neurodevelopmental outcome..


Asunto(s)
Recién Nacido de muy Bajo Peso , Leche Humana , Lactancia Materna , Niño , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Madres , Donantes de Tejidos
5.
J Pediatr ; 228: 44-52.e3, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32916143

RESUMEN

OBJECTIVE: To assess serial secretory activation biomarker concentrations (sodium [Na], potassium [K], Na:K, protein, lactose, and citrate) in mother's own milk (MOM) from breast pump-dependent mothers of preterm infants to determine associations with coming to volume (CTV), defined as producing at least 500 mL/day MOM by day 14 postpartum. STUDY DESIGN: We collected serial MOM samples and pumped MOM volume data for 14 days postpartum in mothers who delivered at <33 weeks of gestation. Regression models and the Mann-Whitney U test were used to evaluate associations. RESULTS: Among 40 mothers, 39 (mean gestational age, 28.8 weeks; 67% overweight/obese; 59% nonwhite) had paired MOM volume and biomarker data; 33% achieved CTV between postpartum days 6 and 14. In univariate models, MOM Na on postpartum day 5 and Na:K on days 3 and 5 were associated with CTV. Mothers achieving CTV were more likely to have postpartum Na:K ≤1 on day 3 (75% vs 25%; P = .06) and ≤0.8 on day 5 (69% vs 10%; P < .01). In a multivariable regression model, day 5 Na:K (1 unit decrease in Na:K: OR, 18.7; 95% CI, 1.13-311.41; P = .049) and maternal prepregnancy body mass index (BMI) (1 unit increase in BMI: OR, 0.88; 95% CI, 0.78-0.99; P = .04) were associated with CTV between postpartum days 6 and 14. CONCLUSIONS: Secretory activation and CTV were compromised in breast pump-dependent mothers with preterm delivery. CTV was predicted by MOM Na level and Na:K. These biomarkers have potential as objective point-of-care measures to detect potentially modifiable lactation problems in a high-risk population.


Asunto(s)
Lactancia Materna/métodos , Extracción de Leche Materna/métodos , Recién Nacido de muy Bajo Peso , Leche Humana/química , Madres , Adulto , Biomarcadores/metabolismo , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Estudios Retrospectivos
6.
Pediatr Res ; 89(2): 344-352, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33188286

RESUMEN

Very low birth weight (VLBW; <1500 g birth weight) infants are substantially more likely to be born to black than to non-black mothers, predisposing them to potentially preventable morbidities that increase the risk for costly lifelong health problems. Mothers' own milk (MOM) may be considered the ultimate "personalized medicine" since milk composition and bioactive components vary among mothers and multiple milk constituents provide specific protection based on shared exposures between mother and infant. MOM feedings reduce the risks and associated costs of prematurity-associated morbidities, with the greatest reduction afforded by MOM through to NICU discharge. Although black and non-black mothers have similar lactation goals and initiation rates, black VLBW infants are half as likely to receive MOM at NICU discharge in the United States. Black mothers are significantly more likely to be low-income, single heads of household and have more children in the home, increasing the burden of MOM provision. Although rarely considered, the out-of-pocket and opportunity costs associated with providing MOM for VLBW infants are especially onerous for black mothers. When MOM is not available, the NICU assumes the costs of inferior substitutes for MOM, contributing further to disparate outcomes. Novel strategies to mitigate these disparities are urgently needed. IMPACT: Mother's own milk exemplifies personalized medicine through its unique biologic activity. Hospital factors and social determinants of health are associated with mother's own milk feedings for very low-birth-weight infants in the neonatal intensive care unit. Notably, out-of-pocket and opportunity costs associated with providing mother's own milk are borne by mothers. Conceptualizing mother's own milk feedings as an integral part of NICU care requires consideration of who bears the costs of MOM provision-the mother or the NICU?


Asunto(s)
Negro o Afroamericano , Lactancia Materna , Disparidades en Atención de Salud , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Unidades de Cuidado Intensivo Neonatal , Leche Humana , Determinantes Sociales de la Salud , Factores Socioeconómicos , Factores de Edad , Peso al Nacer , Lactancia Materna/economía , Lactancia Materna/etnología , Desarrollo Infantil , Femenino , Edad Gestacional , Costos de la Atención en Salud , Gastos en Salud , Disparidades en Atención de Salud/economía , Disparidades en Atención de Salud/etnología , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Estado Nutricional , Valor Nutritivo , Nacimiento Prematuro , Factores Raciales , Determinantes Sociales de la Salud/economía , Determinantes Sociales de la Salud/etnología , Estados Unidos
7.
J Pediatr ; 224: 57-65.e4, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32682581

RESUMEN

OBJECTIVE: To assess the cost-effectiveness of mother's own milk supplemented with donor milk vs mother's own milk supplemented with formula for infants of very low birth weight in the neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective analysis of 319 infants with very low birth weight born before (January 2011-December 2012, mother's own milk + formula, n = 150) and after (April 2013-March 2015, mother's own milk + donor milk, n = 169) a donor milk program was implemented in the NICU. Data were retrieved from a prospectively collected research database, the hospital's electronic medical record, and the hospital's cost accounting system. Costs included feedings and other NICU costs incurred by the hospital. A generalized linear regression model was constructed to evaluate the impact of feeding era on NICU total costs, controlling for neonatal and sociodemographic risk factors and morbidities. An incremental cost-effectiveness ratio was calculated for each morbidity that differed significantly between feeding eras. RESULTS: Infants receiving mother's own milk + donor milk had a lower incidence of necrotizing enterocolitis (NEC) than infants receiving mother's own milk + formula (1.8% vs 6.0%, P = .048). Total (hospital + feeding) median costs (2016 USD) were $169 555 for mother's own milk + donor milk and $185 740 for mother's own milk + formula (P = .331), with median feeding costs of $1317 and $936, respectively (P < .001). Mother's own milk + donor milk was associated with $15 555 lower costs per infant (P = .045) and saved $1812 per percentage point decrease in NEC incidence. CONCLUSIONS: The additional cost of a donor milk program was small compared with the cost of a NICU hospitalization. After its introduction, the NEC incidence was significantly lower with small cost savings per case. We speculate that NICUs with greater NEC rates may have greater cost savings.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal/economía , Bancos de Leche Humana/economía , Leche Humana , Lactancia Materna/economía , Análisis Costo-Beneficio , Humanos , Fórmulas Infantiles/economía , Recién Nacido , Enfermedades del Prematuro/prevención & control , Recién Nacido de muy Bajo Peso , Estudios Retrospectivos
8.
J Pediatr ; 227: 128-134.e2, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32553865

RESUMEN

OBJECTIVE: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC). STUDY DESIGN: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition. RESULTS: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001). CONCLUSIONS: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.


Asunto(s)
Antibacterianos/administración & dosificación , Enterocolitis Necrotizante/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Bases de Datos Factuales , Enterocolitis Necrotizante/prevención & control , Femenino , Humanos , Incidencia , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/prevención & control , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino
9.
Pediatr Res ; 88(Suppl 1): 21-24, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32855508

RESUMEN

High-dose mother's own milk (MOM) feedings during the first 14 days post birth reduce the risk of necrotizing enterocolitis in very low birthweight (VLBW; <1500 g birthweight). However, high-dose MOM feedings are only possible if mothers provide sufficient quantities of MOM in a timely manner, and data indicate that the lack of MOM during the early post-birth period is a global problem. This paper reviews the modifiable and unmodifiable barriers to accessing adequate quantities of MOM during the early post-birth period and proposes evidence-based strategies to increase and improve the use of MOM during the neonatal intensive care unit (NICU) hospitalization with an emphasis on the critical first 2 weeks post birth.


Asunto(s)
Enterocolitis Necrotizante/terapia , Enfermedades del Recién Nacido/terapia , Leche Humana , Neonatología/métodos , Lactancia Materna , Medicina Basada en la Evidencia , Accesibilidad a los Servicios de Salud , Disparidades en el Estado de Salud , Disparidades en Atención de Salud , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Cuidado Intensivo Neonatal , Madres , Periodo Posparto , Riesgo
10.
J Pediatr Nurs ; 50: 5-13, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31670137

RESUMEN

PROBLEM: Breastfed infants experience less severe infections while actively breastfeeding. However, little is known about whether a history of prior breastfeeding affects severity of illness. Therefore, the purpose of this integrative review was to examine the relationship between previous exposure to mother's own milk (MOM) feeding and severity of respiratory infectious illness in infants and children. ELIGIBILITY CRITERIA: Studies meeting the following criteria were included: human subjects, term birth, ages 0-35 months at time of study, diagnosis of pneumonia, bronchiolitis or croup, MOM feeding, and statistical analyses reporting separate respiratory infectious illness outcomes when combined with other infections. SAMPLE: Twelve articles met eligibility criteria. RESULTS: Major findings were inconsistent definitions of both dose and exposure period of breastfeeding and the severity of illness. In particular, the severity of illness measure was limited by the use of proxy variables such as emergency room visits or hospitalizations that lacked reliability and validity. However, given this limitation, the data suggested that exclusive breastfeeding for four to six months was associated with reduced severity of illness as measured by frequency of visits to the primary care provider office, emergency department or hospitalization. CONCLUSIONS: Future research in this area should incorporate reliable and valid measures of MOM dose and exposure period and severity of illness outcomes in the critically ill child. IMPLICATIONS: Among many positive outcomes associated with breastfeeding, an additional talking point for encouragement of exclusive breastfeeding for four to six months may be protective against severe respiratory infectious illness after cessation of breastfeeding.


Asunto(s)
Lactancia Materna , Leche Humana , Infecciones del Sistema Respiratorio/epidemiología , Enfermedad Aguda , Preescolar , Humanos , Incidencia , Lactante , Recién Nacido , Índice de Severidad de la Enfermedad
11.
Pediatr Res ; 86(6): 786, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31534188

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

12.
Pediatr Res ; 85(5): 662-670, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30679795

RESUMEN

BACKGROUND: Despite high initiation rates for mother's own milk (MOM) provision, MOM feeding at discharge from the neonatal intensive care unit (NICU) drops precipitously and reveals a racial/ethnic disparity. This study sought to identify factors that (1) predict MOM feeding at NICU discharge, and (2) mediate racial/ethnic disparity in MOM feeding at discharge. METHODS: Secondary analysis of prospective cohort study of 415 mothers and their very low birth weight infants. Variables were grouped into five categories (demographics, neighborhood structural, social, maternal health, and MOM pumping). Significant predictors from each category were entered into a multivariable logistic regression model. RESULTS: Although 97.6% of infants received MOM feedings, black infants were significantly less likely to receive MOM feeding at discharge. Positive predictors were daily pumping frequency, reaching pumped MOM volume ≥500 mL/day by 14 days, and maternal age. Negative predictors were low socioeconomic status (SES) and perceived breastfeeding support from the infant's maternal grandmother. Low SES, maternal age, and daily pumping frequency mediated the racial/ethnic differences. CONCLUSIONS: Multiple potentially modifiable factors predict MOM feeding at NICU discharge. Importantly, low SES, pumping frequency, and maternal age were identified as the mediators of racial and ethnic disparity. Strategies to mitigate the effects of modifiable factors should be developed and evaluated in future research.


Asunto(s)
Lactancia Materna/etnología , Lactancia Materna/estadística & datos numéricos , Etnicidad , Leche Humana , Apoyo Social , Adulto , Escolaridad , Femenino , Humanos , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Cuidado Intensivo Neonatal , Masculino , Edad Materna , Madres , Alta del Paciente , Estudios Prospectivos , Clase Social , Adulto Joven
13.
J Pediatr ; 202: 23-30.e1, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30170862

RESUMEN

OBJECTIVE: To identify factors associated with prolonged maternal breast milk (BM) provision in very low birth weight (VLBW) infants. STUDY DESIGN: This was a cohort study of VLBW infants who initially received maternal BM and were born at one of 197 neonatal intensive care units managed by the Pediatrix Medical Group from 2010 to 2012. We used multivariable logistic regression to identify demographic, clinical, and maternal factors associated with provision of maternal BM on day of life (DOL) 30 and at discharge. RESULTS: Median gestational age for all infants was 28 weeks (25th, 75th percentiles: 26, 30), and median maternal age was 28 years (23, 33). Of 8806 infants, 6261 (71%) received maternal BM on DOL 30, and 4003 of 8097 (49%) received maternal BM at discharge to home. Predictors of maternal BM provision at DOL 30 included increased maternal age, white maternal race, absence of history of necrotizing enterocolitis or late-onset sepsis, higher household income, lower education level, lack of donor BM exposure, and lower gestational age. CONCLUSIONS: Our results suggest that maternal-infant demographic and clinical factors and household neighborhood socioeconomic characteristics were associated with provision of maternal BM at 30 postnatal days to VLBW infants. Identification of these factors allows providers to anticipate mothers' needs and develop tailored interventions designed to improve rates of prolonged maternal BM provision and infant outcomes.


Asunto(s)
Lactancia Materna/estadística & datos numéricos , Recién Nacido de muy Bajo Peso , Adulto , Estudios de Cohortes , Escolaridad , Femenino , Edad Gestacional , Humanos , Renta , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , Edad Materna , North Carolina , Población Blanca , Adulto Joven
14.
J Pediatr Gastroenterol Nutr ; 66(6): e153-e157, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29470288

RESUMEN

OBJECTIVES: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract. METHODS: Fully differentiated Caco-2 cells were exposed to digested HM (n = 10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F2-isoprostane, and cytotoxicity by released lactate dehydrogenase. RESULTS: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses. CONCLUSIONS: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis.


Asunto(s)
Muerte Celular/inmunología , Enterocolitis Necrotizante/prevención & control , Enfermedades del Prematuro/prevención & control , Recien Nacido Prematuro/inmunología , Inflamación/prevención & control , Mucosa Intestinal/inmunología , Leche Humana/inmunología , Biomarcadores/metabolismo , Células CACO-2 , Enterocolitis Necrotizante/etiología , Enterocolitis Necrotizante/inmunología , Enterocolitis Necrotizante/metabolismo , Humanos , Recién Nacido , Recien Nacido Prematuro/metabolismo , Enfermedades del Prematuro/etiología , Enfermedades del Prematuro/inmunología , Enfermedades del Prematuro/metabolismo , Inflamación/etiología , Inflamación/inmunología , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Lipopolisacáridos , Leche Humana/metabolismo , Estrés Oxidativo/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
16.
J Pediatr Gastroenterol Nutr ; 62(2): 292-303, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26230901

RESUMEN

OBJECTIVES: The aim of the present study was to examine the changes in bacteria in hospitalized preterm infants during the first month of life. METHODS: Rectal swabs were collected daily from 12 preterm infants. DNA was extracted from swabs from day of birth and weekly thereafter. Bacterial taxa were identified with next generation sequencing using universal bacterial primers targeted at the 16S ribosomal DNA on a 454 Roche titanium platform. Sequences were clustered into operational taxonomic units, and taxonomy was assigned against the Greengenes databank using Quantitative Insights Into Microbial Ecology version 1.4. Quantitative polymerase chain reaction was used to determine the abundance of Bifidobacterium spp. Functional assessment of the microbiome was performed with Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). RESULTS: Average birth weight and gestational age were 1055 g and 28 weeks, respectively. There were 6 to 35 different bacterial families identified in the day-of-birth samples, unrelated to the mode of delivery. Richness decreased through hospitalization (week 1, 16.9 ±â€Š7.7 vs weeks 3-5, 10.7 ±â€Š3.4, P < 0.001). The Shannon diversity index demonstrated the lowest diversity at birth, an increase at week 2, followed by a rapid decline at weeks 3 to 5, suggesting the development of a more uniform microbiota composition after 2 weeks of stay at a neonatal intensive care unit. Enterobacteriaceae, Staphylococcaceae, and Enterococcaceae constituted the majority of the bacterial families. Bifidobacterium spp were infrequently detected at extremely low levels. PICRUSt analysis revealed the enhancement of peroxisome, PPAR, and adipocytokine signaling; plant-pathogen interaction; and aminobenzoate degradation pathways in week 1 samples. CONCLUSIONS: Our results suggest that although preterm infants have individualized microbiota that are detectable at birth, the differences decrease during the neonatal intensive care unit hospitalization with increasing prominence of pathogenic microbiota.


Asunto(s)
Bacterias/crecimiento & desarrollo , Microbioma Gastrointestinal , Tracto Gastrointestinal/microbiología , Hospitalización , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal , Peso al Nacer , ADN Bacteriano/análisis , Heces/microbiología , Femenino , Edad Gestacional , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Filogenia , ARN Ribosómico 16S
17.
Am J Perinatol ; 33(8): 738-44, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26890439

RESUMEN

Objective To evaluate the relative impact of maternal education level (MEL) on cognitive, language, and motor outcomes at 20 months' corrected age (CA) in preterm infants. Study Design A total of 177 preterm infants born between 2008 and 2010 were tested at 20 months' CA using the Bayley Scales of Infant and Toddler Development-III. Multiple regression analyses were done to determine the relative impact of MEL on cognitive, language, and motor scores. Results Infants born to mothers with high school MEL were 3.74 times more likely to have a subnormal motor index, while those born to mothers with some college and graduate school MEL had reduced odds (0.36 and 0.12, respectively) of having subnormal language index at 20 months. In linear regression, MEL was the strongest predictor of cognitive, language, and motor scores, and graduate school MEL was associated with increases in cognitive, motor, and language scores of 8.49, 8.23, and 15.74 points, respectively. Conclusions MEL is the most significant predictor of cognitive, language, and motor outcome at 20 months' CA in preterm infants. Further research is needed to evaluate if targeted interventions that focus on early childhood learning and parenting practices can ameliorate the impact of low MEL.


Asunto(s)
Desarrollo Infantil , Lenguaje Infantil , Cognición , Escolaridad , Recien Nacido Prematuro/crecimiento & desarrollo , Actividad Motora , Adolescente , Adulto , Chicago , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Modelos Lineales , Masculino , Análisis Multivariante , Estudios Retrospectivos , Adulto Joven
18.
Am J Physiol Gastrointest Liver Physiol ; 309(3): G171-80, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26045614

RESUMEN

Human milk contains biologically important amounts of transforming growth factor-ß2 isoform (TGF-ß2), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-ß2 can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-ß bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-ß2 (rTGF-ß2) to milk prior to feeding. Milk-borne TGF-ß bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-ß2 were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-ß2 (20-40 nM) to human preterm milk samples failed to increase TGF-ß bioactivity in milk. Milk-borne TGF-ß2 was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-ß2, and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-κB activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-ß2 and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk.


Asunto(s)
Condroitinasas y Condroitín Liasas/metabolismo , Enterocolitis Necrotizante , Leche Humana , Factor de Crecimiento Transformador beta2/metabolismo , Animales , Antiinflamatorios/metabolismo , Disponibilidad Biológica , Línea Celular , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Enterocolitis Necrotizante/metabolismo , Enterocolitis Necrotizante/prevención & control , Humanos , Recién Nacido , Recien Nacido Prematuro , Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Activación de Macrófagos/fisiología , Ratones , Leche Humana/enzimología , Leche Humana/metabolismo , FN-kappa B/metabolismo , Proteínas Recombinantes/metabolismo
19.
Acta Paediatr ; 104(7): e306-13, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25684177

RESUMEN

AIM: To examine associations between maternal neonatal intensive care unit (NICU) visitation rates, maternal psychological distress ('distress') and preterm infant outcome post-NICU discharge in a contemporary cohort of very low birthweight (VLBW) infants. METHODS: This was a prospective study of 69 mothers and their VLBW infants. Distress was assessed 1-month postbirth, 2 weeks prior to NICU discharge and after NICU discharge at 4-month corrected age (CA). Maternal NICU visitation rates were calculated for the first 2 weeks and 1-month postbirth as well as for the entire NICU hospitalization. Regression analyses adjusted for the impact of (i) maternal and infant characteristics and distress on maternal visitation rates and (ii) the impact of visitation on long-term maternal distress and rates of infant clinic attendance and rehospitalization. RESULTS: Greater number of children in the home, maternal exposure to a greater number of potentially traumatic events prior to childbirth and lower maternal anxiety consistently predicted lower visitation rate. Lower maternal visitation rate predicted higher maternal depression scores at infants' 4-month CA visit. Maternal NICU visitation rate did not predict post-NICU discharge infant clinic attendance or rehospitalization. CONCLUSION: Distress is an important predictor of visitation. In turn, visitation is associated with long-term maternal distress.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Conducta Materna/psicología , Madres/psicología , Estrés Psicológico/psicología , Adulto , Atención Ambulatoria/estadística & datos numéricos , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Adulto Joven
20.
J Perinatol ; 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851855

RESUMEN

OBJECTIVE: Pumping studies in mothers of preterm infants are limited by self-reported pumping behaviors and non-objective measures of pumped milk volume and secretory activation (SA). METHODS: Non-randomized observational study of first 14 days postpartum in 29 mothers of preterm infants. Smart pumps measured and stored pumping behaviors and pumped milk volume. Selective ion electrodes measured sodium and sodium:potassium ratio to determine SA. Generalized estimating equations, cluster analyses and multivariate regression were used. RESULTS: SA was delayed (median 5.8 days) and impermanent. Each additional daily pumping increased odds of SA within 2 days by 48% (p = 0.01). High-intensity pumping mothers (N = 17) had greater daily and cumulative pumped milk volume than low-intensity pumping mothers (N = 12). Pumping variables showed daily changes in the first week, then plateaued. CONCLUSION: The first week postpartum is critical for optimizing pumping behaviors. Accurate, objective measures of pumping behaviors, pumped milk volume and SA are a research priority.

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