Clinical, Virologic and Immunologic Correlates of Breast Milk Acquired Cytomegalovirus (CMV) Infections in Very Low Birth Weight (VLBW) Infants in a Newborn Intensive Care Unit (NICU) Setting.

Cytomegalovirus (CMV) infections acquired by very-low-birthweight (VLBW) infants are incompletely characterized. To examine CMV transmission in VLBW infants, we evaluated maternal DNAlactia, infant DNAemia, and presence of clinical disease in a blinded study in VLBW infants in our newborn intensive care unit (NICU). To examine these issues, 200 VLBW infants were enrolled in a surveillance study, with weekly breast milk and infant whole blood samples collected, as available. Virologic (breast milk and infant whole blood real time PCR) and immunologic (IgG, IgM, and IgG avidity) correlates were evaluated. A chart review examined whether infants had symptoms compatible with CMV disease. DNAlactia was identified in 65/150 (43%) of lactating mothers. Nine CMV infections were identified in 9/75 CMV-exposed infants (12% of exposed infants). A higher median breast milk viral load (DNAlactia) correlated with an increased likelihood of DNAemia (p = 0.05). Despite potential symptoms compatible with CMV infection, clinicians had not considered the diagnosis of CMV in 6/9 cases (66%). All of these infants had chronic lung disease at discharge. There was no correlation between IgG antibody titer or IgG avidity index and the likelihood of transmission or CMV disease. In conclusion, in VLBW infants receiving milk from seropositive mothers, CMV infections are commonly acquired, and are frequently unrecognized. Future studies are needed to determine whether routine surveillance for CMV of either breast milk or infant plasma is beneficial in preventing or recognizing infection.

Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders.

Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.

Nutritional Factors Associated with Late-Onset Sepsis in Very Low Birth Weight Newborns.

BACKGROUND: Delayed onset of minimal enteral nutrition compromises the immune response of preterm infants, increasing the risk of colonization and clinical complications (e.g., late-onset sepsis). This study aimed to analyze associations between late-onset sepsis in very low birth weight infants (<1500 g) and days of parenteral nutrition, days to reach full enteral nutrition, and maternal and nutritional factors. METHODS: A cross-sectional study was carried out with very low birth weight infants admitted to a neonatal intensive care unit (NICU) of a reference maternity hospital of high-risk deliveries. Data regarding days of parenteral nutrition, days to reach full enteral nutrition, fasting days, extrauterine growth restriction, and NICU length of stay were extracted from online medical records. Late-onset sepsis was diagnosed (clinical or laboratory) after 48 h of life. Chi-squared, Mann-Whitney tests, and binary logistic regression were applied. RESULTS: A total of 97 preterm infants were included. Of those, 75 presented late-onset sepsis with clinical (n = 40) or laboratory (n = 35) diagnosis. Maternal urinary tract infection, prolonged parenteral nutrition (>14 days), and extrauterine growth restriction presented 4.24-fold, 4.86-fold, and 4.90-fold higher chance of late-onset sepsis, respectively. CONCLUSION: Very low birth weight infants with late-onset sepsis had prolonged parenteral nutrition and took longer to reach full enteral nutrition. They also presented a higher prevalence of extrauterine growth restriction than infants without late-onset sepsis.

The association of γδ-T cells with bronchopulmonary dysplasia in premature infants.

BACKGROUND: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it. OBJECTIVE: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants. MATERIALS AND METHOD: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth. CONCLUSIONS: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.

Plasma cytokine profiles in very preterm infants with late-onset sepsis.

INTRODUCTION: Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood. AIMS: To characterise plasma pro- and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS). METHODS: In this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay. RESULTS: IL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1ß, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without. CONCLUSION: Very preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants.

Postnatal probiotics and allergic disease in very preterm infants: Sub-study to the ProPrems randomized trial.

BACKGROUND: Probiotic supplementation to mothers and/or their term-born infants has been suggested to prevent allergic disease, in particular eczema; however, no studies have investigated probiotics for prevention of allergic diseases in very preterm infants. We evaluated the effect of a postnatal probiotic combination on development of allergic diseases in very preterm infants. METHODS: This sub-study was an a priori secondary outcome of the ProPrems multi-center, double-blind, placebo-controlled randomized trial (ANZCTR:12607000144415). ProPrems randomized 1099 very preterm infants to receive a probiotic combination or placebo from soon after birth until discharge from hospital or term corrected age (CA), whichever was earlier. Allergic disease (eczema, atopic eczema, food allergy, wheeze, atopic sensitization) was assessed in a subgroup of ProPrems infants (n = 281) as close to 12 months CA as possible by questionnaire, clinical examination, and skin prick tests to common allergens. RESULTS: There was no difference in eczema incidence between the probiotic and placebo groups (35[30%] of 118 infants vs 37[27%] of 137 infants, respectively, absolute difference 2.65%, 95% CI -8.45 to 13.75). Similarly, the incidence of atopic eczema (6[5%] of 118 vs 3[2%] of 137), food allergy (4[3%] of 124 vs 2[1%] of 154), wheeze (39[31%] of 127 vs 45[29%] of 154), and atopic sensitization (14[13%] of 106 vs 13[11%] of 123) were similar between the probiotic and placebo groups. CONCLUSION: This study found no effect of postnatal administration of a probiotic combination on the incidence of allergic diseases or atopic sensitization in the first 2 years of life in children born very preterm. Evidence that probiotics are effective for prevention of allergic disease in premature infants remains lacking; adequately powered randomized controlled trials evaluating probiotic supplementation for allergy prevention in very preterm infants are needed.

Early oral colostrum administration in preterm infants.

BACKGROUND: Early administration of colostrum may provide preterm infants with immune components. Previous studies illustrating the effects of oral colostrum (OC) have been confounded by the coincidence of enteral feedings. OBJECTIVE: To quantify OC absorption, as measured by urinary sIgA and lactoferrin, in preterm infants prior to enteral feedings. MATERIALS AND METHODS: Colostrum was obtained from mothers delivering infants ≤32 weeks and ≤1500 g. sIgA and lactoferrin were measured in infant urine, and microflora in saliva and tracheal aspirates were characterized. RESULTS: Urinary sIgA and lactoferrin were significantly greater in infants receiving OC by syringe compared to swab (p < 0.002). Urinary sIgA correlated with the total number of doses in 72 h (R2 = 43%, p < 0.01). CONCLUSIONS: Administration of OC by syringe and higher cumulative dose are associated with increased absorption of sIgA and lactoferrin, and early dosing may contribute to a more diverse tracheal microbiome.

An exclusive human milk diet for very low birth weight newborns-A cost-effectiveness and EVPI study for Germany.

OBJECTIVES: Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow's milk-based fortifiers in very low birth weight newborns. METHODS: A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values. RESULTS: In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent. CONCLUSION: Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany.

Facilitating Colostrum Collection by Hospitalized Women in the Early Postpartum Period for Infant Trophic Feeding and Oral Immune Therapy.

Administration of colostrum for early trophic feedings and colostrum oral immune therapy for neonates in the NICU is essential to enhance gut maturation and lower risk of infections. However, it is often difficult for women to collect early colostrum because of its thick viscosity and low volume. Women may be unable to sit upright during pumping sessions because of postsurgical pain, acute or chronic illness, or birth complications and may need assistance. In this article, we describe specific techniques that providers can use to help women to collect colostrum when they are unable to accomplish collection on their own. Helping women collect and administer colostrum to their neonates in the NICU may engage and motivate them to continue to pump and provide breast milk for their hospitalized neonates.

Effect of oropharyngeal colostrum therapy in the prevention of necrotising enterocolitis among very low birthweight neonates: A meta-analysis of randomised controlled trials.

BACKGROUND: Necrotising enterocolitis (NEC) is one of the most common life-threatening emergencies of the gastrointestinal tract in preterm neonates. The present study aimed to determine the efficacy of oropharyngeal colostrum with respect to reducing NEC in preterm neonates. METHODS: A literature search was conducted for various randomised control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE and ongoing clinical trials. Randomised or quasi-randomised trials comparing oropharyngeal colostrum versus placebo in neonates (birthweight ≤ 1500 g or gestational age ≤ 32 weeks) were included in the review. The methodological quality of each trial was independently reviewed by the authors. For categorical and continuous variables, typical estimates for relative risk and typical estimates for weighted mean difference were calculated, respectively. A random effect model was assumed for meta-analysis. RESULTS: In total, four eligible trials were included in the review. Oropharyngeal colostrum therapy was not associated with a statistically significant reduction in the incidence of NEC stage ≥2 [typical relative risk (RR) = 0.64; 95% confidence interval (CI) = 0.27-1.49], mortality from any cause (typical RR = 0.86; 95% CI = 0.15-4.80) and time to reach full feed [typical weighted mean difference (WMD) = -3.26; 95% CI = -8.87 to 2.35]. Duration of hospital stay was significantly less in the control group (typical WMD = 9.77; 95% CI = 3.96-15.59). CONCLUSIONS: The current evidence is insufficient for recommending oropharyngeal colostrum as a routine clinical practice in the prevention of NEC. We emphasise the need for large randomised controlled trials with an adequate sample size and validated clinical outcomes in preterm neonates.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants.

INTRODUCTION: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. OBJECTIVES: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. METHODS: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight <1500g and who were in follow-up at the outpatient clinic for preterm infants at the institution and other group of infants born at full-term. Infants with malformations, primary immunodeficiency diseases, born to HIV-positive mothers or who had received plasma or immunoglobulin transfusions five months before or three weeks after vaccination were excluded. Plasma antibodies were measured by ELISA and factors associated with antibody levels were assessed by linear regression. RESULTS: Sixty-five premature and 56 full-term infants were included. The percentage of immune individuals after vaccination against measles (100% vs. 100%) and varicella (92.5% vs. 93.2%) were similar in both groups, as well as the antibody levels against measles (2.393 vs. 2.412UI/mL; p=0.970) and varicella (0.551 vs. 0.399UI/mL; p=0.114). Use of antenatal corticosteroids decreased measles antibody levels whereas breastfeeding for more than six months increased varicella antibody levels. CONCLUSIONS: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

ABSTRACT Introduction: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. Objectives: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. Methods: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight <1500 g and who were in follow-up at the outpatient clinic for preterm infants at the institution and other group of infants born at full-term. Infants with malformations, primary immunodeficiency diseases, born to HIV-positive mothers or who had received plasma or immunoglobulin transfusions five months before or three weeks after vaccination were excluded. Plasma antibodies were measured by ELISA and factors associated with antibody levels were assessed by linear regression. Results: Sixty-five premature and 56 full-term infants were included. The percentage of immune individuals after vaccination against measles (100% vs. 100%) and varicella (92.5% vs. 93.2%) were similar in both groups, as well as the antibody levels against measles (2.393 vs. 2.412 UI/mL; p = 0.970) and varicella (0.551 vs. 0.399 UI/mL; p = 0.114). Use of antenatal corticosteroids decreased measles antibody levels whereas breastfeeding for more than six months increased varicella antibody levels. Conclusions: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

Human-Based Human Milk Fortifier as Rescue Therapy in Very Low Birth Weight Infants Demonstrating Intolerance to Bovine-Based Human Milk Fortifier.

OBJECTIVE: To describe the results of utilizing a human milk-based human milk fortifier (HMHMF) as rescue therapy to meet nutritional requirements in very low birth weight and preterm infants demonstrating feeding intolerance to bovine-based human milk fortifier (BHMF) in the Canadian Neonatal Intensive Care Unit (NICU) setting. MATERIALS AND METHODS: At two Level III NICUs in Winnipeg, MB, Canada, a rescue protocol was implemented to provide HMHMF for infants demonstrating intolerance to BHMF. To qualify for rescue, infants were required to experience two episodes of significant gastrointestinal (GI) symptoms associated with fortification with BHMF. A case series report was conducted retrospectively examining the success of rescue therapy, growth rates, protein, and calorie intakes before and after initiation of HMHMF in seven infants. RESULTS: Seven infants (birth weight 723 ± 247 g, gestation 25.3 ± 3.4 weeks) were treated with rescue fortification with HMHMF. All infants were transitioned off parenteral nutrition (PN) without relapse of GI symptoms. Growth rate, protein, and calorie intakes improved with the use of HMHMF. CONCLUSIONS: Very low birth weight and preterm infants with GI intolerance to BHMF were successfully rescued with use of HMHMF. Improvements in growth were achieved without need for supplementation with PN through achievement of sufficient enteral calorie and protein intakes.

Oropharyngeal Colostrum Administration in Very Low Birth Weight Infants: A Randomized Controlled Trial.

OBJECTIVES: Studies have confirmed the safety of oropharyngeal administration of colostrum in very low birth weight infants. However, the effect of oropharyngeal administration of colostrum on immune system is inconclusive. This study aims to evaluate the effect of oropharyngeal administration of colostrum on secretory immunoglobulin A and lactoferrin in very low birth weight infants. DESIGN: Randomized controlled trial. SETTING: Forty-bedded neonatal ICU in a university children's hospital in the People's Republic of China. PATIENTS: Very low birth weight infants were allocated to the study group (n = 32) and control group (n = 32). INTERVENTION: The intervention was oropharyngeal administration of 0.2 mL of their mother's colostrum every 4 hours for 7 days. The control group received saline solution. MEASUREMENTS AND MAIN RESULTS: Secretory immunoglobulin A and lactoferrin in urine and saliva were measured within 24 hours of life (baseline) and at 7 and 21 days. Primary outcomes were changes of secretory immunoglobulin A and lactoferrin in urine and saliva between baseline and at 7 and 21 days. Infant's clinical data were also collected during hospitalization. Change from baseline in lactoferrin in saliva at 7 days (5.18 ± 7.07 vs -1.74 ± 4.67 µg/mL; p < 0.001) and 21 days (5.31 ± 9.74 vs -1.17 ± 10.38 µg/mL; p = 0.02) shows statistic difference. No differences were found of lactoferrin in urine and also no differences of secretory immunoglobulin A in urine and saliva. There were also no differences between days to full enteral feeding, occurrence rate of clinical sepsis, proven sepsis, and necrotizing enterocolitis. CONCLUSIONS: Oropharyngeal administration of colostrum can increases the level of lactoferrin in saliva in very low birth weight infants. No effect could be documented of secretory immunoglobulin A and lactoferrin in urine. Larger trials are needed to better describe the benefit of oropharyngeal administration of colostrum, if any, in very low birth weight infants.

Systematic review and meta-analysis of human milk intake and retinopathy of prematurity: a significant update.

OBJECTIVE: Two recent meta-analyses have studied the association of exclusive or mainly human milk intake (HMI) on retinopathy of prematurity (ROP). One of these meta-analysis found a protective effect of only or mainly HMI on Severe ROP but not on any stage ROP. However, both these meta-analyses did not find protection from any stage ROP or Severe ROP with any amount of HMI. The objective of this study was to study the association between any amount of HMI and the development of All ROP and Severe ROP in very-low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI) by systematic review using PRISMA-P guidelines and meta-analysis. STUDY DESIGN: Exposure, controls and outcomes studied were any amount of HMI vs no HMI and All ROP/Severe ROP in VLBWI/ELBWI. All ROP was defined as all stages of ROP pooled together, and Severe ROP as ⩾stage 3 ROP and ROP requiring intervention. Results and effect sizes are expressed as odds ratio (OR), relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence intervals (95% CI). Data sources used were PubMed, MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, Scopus and CINAHL until 24 April 2015. Extracted data were pooled using a fixed effects model. Heterogeneity was assessed. Sensitivity analysis was performed. RESULTS: Five hundred nine of 1701 infants who received any amount of HMI developed All ROP vs 310 of 760 infants without HMI developed All ROP with a pooled OR 0.63* (0.51,0.78), RR 0.76* (0.67,0.86) and RD -0.09* (-0.13,-0.05). The NNT with any amount of HMI was 11* (8,20) (*P<0.0001) to prevent one case of All ROP. 204 of 2465 infants who received any amount of HMI developed Severe ROP vs 85 of 764 infants without HMI developed Severe ROP with a pooled OR 0.74* (0.56,0.98), RR 0.77* (0.60,0.98) and RD -0.03* (-0.05,-0.00). The NNT with any amount of HMI was 33* (*P=0.04) to prevent one case of Severe ROP. CONCLUSION: Any amount of HMI is strongly associated with the protection from All ROP and Severe ROP.

Efectos de la administración de calostro orofaríngeo en recién nacidos prematuros sobre los niveles de inmunoglobulina A.

Introducción: el recién nacido prematuro de muy bajo peso (RNMBP) es inmunológicamente inmaduro y además presenta una alteración de las barreras naturales de defensa. Objetivo: evaluar los efectos que pueda tener la administración de calostro orofaríngeo, administrado durante los primeros 15 días posnatales, sobre los niveles de inmunoglobulina A (IgA) sérica en recién nacidos prematuros de muy bajo peso durante el primer mes de vida. Material y métodos: se desarrolló un estudio de intervención no aleatorizado con grupo control, en el que se incluyeron 38 recién nacidos con ≤ 32 + 6 semanas de gestación y/o menores de 1.500 g de peso. Los sujetos recibieron 0,2 ml de calostro de su madre cada 4 h, iniciándose el procedimiento en las primeras 24 h de vida hasta el 15.o día postnatal. Se midieron los niveles de IgA en la sangre al nacimiento, 3. er , 15.o y 30.o días de vida. Se registraron datos perinatales al nacimiento y durante el periodo de seguimiento. Resultados: IgA sérica aumentó de forma estadísticamente significativa en el grupo de intervención (M1 15,84 µg/ml, M2 20,07 µg/ml, M3 23,65 µg/ml, M4 30,34 µg/ml, p 0,001) y en el grupo control (M1 12,48 µg/ml, M2 16,48 µg/ml, p 0,018; M3 19,41 µg/ml, M4 22,48 µg/ml, p 0,001). Al mes de vida, los niveles de IgA sérica fueron significativamente mayores en el grupo de intervención que en el grupo control (p 0,026). Conclusiones: este estudio sugiere que la administración de calostro orofarínge.

Efectos de la administración de calostro orofaríngeo en recién nacidos prematuros sobre los niveles de inmunoglobulina A / Effect of oropharyngeal colostrum administration on immunoglobulin A levels in preterm newborns

Introducción: el recién nacido prematuro de muy bajo peso (RNMBP) es inmunológicamente inmaduro y además presenta una alteración de las barreras naturales de defensa. Objetivo: evaluar los efectos que pueda tener la administración de calostro orofaríngeo, administrado durante los primeros 15 días posnatales, sobre los niveles de inmunoglobulina A (IgA) sérica en recién nacidos prematuros de muy bajo peso durante el primer mes de vida. Material y métodos: se desarrolló un estudio de intervención no aleatorizado con grupo control, en el que se incluyeron 38 recién nacidos con ≤ 32 + 6 semanas de gestación y/o menores de 1.500 g de peso. Los sujetos recibieron 0,2 ml de calostro de su madre cada 4 h, iniciándose el procedimiento en las primeras 24 h de vida hasta el 15.º día postnatal. Se midieron los niveles de IgA en la sangre al nacimiento, 3.er, 15.º y 30.º días de vida. Se registraron datos perinatales al nacimiento y durante el periodo de seguimiento. Resultados: IgA sérica aumentó de forma estadísticamente significativa en el grupo de intervención (M1 15,84 µg/ml, M2 20,07 µg/ml, M3 23,65 µg/ml, M4 30,34 µg/ml, p 0,001) y en el grupo control (M1 12,48 µg/ml, M2 16,48 µg/ml, p 0,018; M3 19,41 µg/ml, M4 22,48 µg/ml, p 0,001). Al mes de vida, los niveles de IgA sérica fueron significativamente mayores en el grupo de intervención que en el grupo control (p 0,026). Conclusiones: este estudio sugiere que la administración de calostro orofaríngeo favorecería el desarrollo del sistema inmunológico de los recién nacidos prematuros y RNMBP a través del aumento de IgA al mes de vida (AU)

Introduction: Very low birth weight (VLBW) newborns have an immature immune system and also disrupted defense natural barriers. Objective: To evaluate the immunologic effects of oropharyngeal colostrum administration to VLBW infants in their first two weeks of life, by assessing IgA serum levels evolution up to one month of life. Material and methods: We conducted an interventional, no randomized, controlled trial recruiting 38 newborns under ≤ 32 + 6 gestational weeks and/or under 1,500 g at birth. Subjects received 0,2 ml of their mother colostrum every 4 hours, starting in the first 24 hours of life, and for a 15 days period. IgA serum levels were measured at birth, 3, 15 and 30 days of life. Perinatal data for the first month of life were registered. Results: Along the first month of life an increase in IgA levels was found in colostrum group (M1 15.84 µg/ml, M2 20.07 µg/ml, M3 23.65 µg ml, M4 30.34 µg/ml, p 0.001) and in control group (M1 12.48 µg/ml, M2 16.48 µg/ml, p 0.018; M3 19.41 µg/ml, M4 22.48 µg/ml, p 0.001). IgA serum levels were statistically increased in colostrum group, in respect to control group at one month of age (p 0.026). Conclusions: Our data suggest that oropharyngeal colostrum administration might facilitate the development of immune system in VLWB infants at one month of age, by increasing IgA serum levels (AU)

Administration of Bifidobacterium breve PS12929 and Lactobacillus salivarius PS12934, two strains isolated from human milk, to very low and extremely low birth weight preterm infants: a pilot study.

The preterm infant gut has been described as immature and colonized by an aberrant microbiota. Therefore, the use of probiotics is an attractive practice in hospitals to try to reduce morbidity and mortality in this population. The objective of this pilot study was to elucidate if administration of two probiotic strains isolated from human milk to preterm infants led to their presence in feces. In addition, the evolution of a wide spectrum of immunological compounds, including the inflammatory biomarker calprotectin, in both blood and fecal samples was also assessed. For this purpose, five preterm infants received two daily doses (~10(9) CFU) of a 1:1 mixture of Bifidobacterium breve PS12929 and Lactobacillus salivarius PS12934. Bacterial growth was detected by culture-dependent techniques in all the fecal samples. The phylum Firmicutes dominated in nearly all fecal samples while L. salivarius PS12934 was detected in all the infants at numerous sample collection points and B. breve PS12929 appeared in five fecal samples. Finally, a noticeable decrease in the fecal calprotectin levels was observed along time.

Association of timing of initiation of breastmilk expression on milk volume and timing of lactogenesis stage II among mothers of very low-birth-weight infants.

BACKGROUND: Feeding breastmilk to premature infants decreases morbidity but is often limited owing to an insufficient milk supply and delayed attainment of lactogenesis stage II. Early initiation of milk expression following delivery has been shown to increase milk production in mothers of very low-birth-weight (VLBW) infants. Although recommendations for milk expression in this population include initiation within 6 hours following delivery, little evidence exists to support these guidelines. This study compared milk volume and timing of lactogenesis stage II in mothers of VLBW infants who initiated milk expression within 6 hours following delivery versus those who initiated expression after 6 hours. SUBJECTS AND METHODS: Forty mothers of VLBW infants were grouped according to when they initiated milk expression following delivery. Group I began milk expression within 6 hours, and Group II began expression after 6 hours. Milk volume was measured daily for the first 7 days and on Days 21 and 42. Timing of lactogenesis stage II was determined through mothers' perceptions of sudden breast fullness. RESULTS: Group I produced more breastmilk during the initial expression session and on Days 6, 7, and 42. No difference in timing of lactogenesis stage II was observed. When mothers who began milk expression prior to 1 hour following delivery were removed from analysis, benefits of milk expression within 6 hours were no longer apparent. CONCLUSIONS: Initiation of milk expression within 6 hours following delivery may not improve lactation success in mothers of VLBW infants unless initiated within the first hour.