Mother's own milk improves health outcomes in infants of all gestational ages. Although pump-dependent mothers of extremely premature infants are at risk of insufficient milk production, whether mother's milk production is impacted by gestational age and pump dependency in mothers of more mature critically ill infants is unknown.To determine whether there is a relationship between gestational age, milk production, and time to secretory activation in mothers delivering a critically ill infant.A convenience sample of 136 pump-dependent mothers whose infants were admitted to the neonatal intensive care unit was enrolled between 2013 and 2016 as part of a quality improvement project. Group 1 (early preterm) delivered infants at 30 to 33 weeks of gestation (n = 41), group 2 (late preterm) 34 to 36 weeks (n = 48), and group 3 (term) 37 weeks and more (n = 47). Milk volume on days 1 to 7 was measured by weighing each vial of expressed milk and compared using general linear mixed-model analysis. Time to the onset of secretory activation was compared using censored regression analysis.Main effect for gestational age controlling for day was statistically significant (P = .0234). The early preterm group produced more milk over the 7-day study than the term (P = .01) and late preterm (P = .02) groups. The early preterm group achieved secretory activation earlier than the late preterm group (adjusted P = .039).Pump-dependent mothers of all infants admitted to the neonatal intensive care unit may be at risk of inadequate milk production and delayed secretory activation and may therefore benefit from early milk production monitoring and lactation support.Further studies should examine targeted interventions to increase milk production in pump-dependent mothers.
Mother's own milk (MOM) is well known to decrease prematurity-related morbidities, yet mothers delivering preterm infants often produce insufficient quantities of milk to provide these benefits. Although a critical need exists for research to support lactation success in this vulnerable population, development and investigation of interventions to increase available MOM for infant consumption requires consistent, valid, and reliable measures of lactation outcomes.The aim of this study was to compare and contrast methods of measuring lactation outcomes in mothers of preterm infants and evaluate their advantages and disadvantages.Measures of lactation outcomes were reviewed and synthesized. Insights on best practices and future research directions are provided.Volume of MOM produced, lactation duration, and time to onset of secretory activation are important measures of lactation success. The most valid and reliable measure of milk production is likely weighing each vial of expressed milk combined with test weighing when infants breastfeed. Measures of lactation duration should include actual days mothers lactated rather than limiting to infant consumption of MOM as a proxy for duration and include not only whether mothers are lactating at infant discharge but whether they are also lactating at other health-relevant time points during hospitalization. Although time to onset of secretory activation is an important lactation outcome, information regarding valid and reliable indicators of onset in women delivering preterm infants is limited, and investigation of such indicators is a research priority. Variables that may affect lactation outcomes, including time to initiation of expression following delivery, duration of expression sessions, expression method, time spent in skin-to-skin care, maternal demographics and comorbidities, as well as maternal intent to lactate, must be considered when researchers investigate lactation outcomes in mothers of very low birth weight infants.Consistent and valid measures of lactation outcomes are required to produce reliable results from which evidence-based practice recommendations can be developed in order to improve lactation success in this vulnerable population.
OBJECTIVES/GOALS: Feeding preterm infants with mother’s own milk (MOM) lowers rates of sepsis, decreases necrotizing enterocolitis, and shortens hospital stay. Our objective is to determine whether a similar microbial diversity to MOM can be obtained when fresh or frozen MOM is inoculated in donor human milk (DHM). METHODS/STUDY POPULATION: Subjects included 12 mothers of infants born 100ml of MOM per day and were excluded if they had taken antibiotics within 3 days of the 1-time pumped MOM sample collection. MOM sample was divided into fresh (processed immediately) and frozen (−20°C) for 24h fractions. MOM was inoculated in DHM [referred to as refaunated milk (RM)] at 10% (RM10) and 30% (RM30) dilutions, then incubated at timepoints: 0h, 2h, 4h at 37°C. At each timepoint, total viable microbial cell counts were performed in differential or selective media along with future 16S rRNA sequencing. RESULTS/ANTICIPATED RESULTS: Microbiota expansion was detected in MOM, RM10 and RM30 over time whether fresh or frozen milk was used as the inoculum. Incubated fresh and frozen MOM had similar bacterial loads when tested on nutrient agar (10^5-10^6 CFU/mL), mannitol salt (10^6 CFU/mL), MacConkey (10^2-10^5 CFU/mL), blood agar (10^6 CFU/mL) and MRS (10^4 CFU/mL) plates. Based on these CFU counts, RM30 incubated for 2h and RM10 at 4h showed similar counts to that of MOM at 0h. DISCUSSION/SIGNIFICANCE OF IMPACT: RM, inoculated with fresh or frozen MOM, obtained a similar microbial count compared to MOM at 0h indicates that fresh or frozen MOM can inoculate DHM. 16s rRNA sequencing is ongoing. Future studies are needed to support an inoculation protocol to be used in clinical practice and human milk banking.
Background: Improved health outcomes for critically ill infants including neurodevelopmental, immunological, and cost benefits are dependent upon the dose and duration of mother's own milk feedings. However, mothers of infants admitted to the neonatal intensive care unit (NICU) must express their milk (pump-dependent) and often struggle with milk production. Purpose: To examine the state of the science on nonpharmacologic modifiable expression factors that may influence milk production in pump-dependent mothers of critically ill infants admitted to the NICU. Data Sources: PubMed, Embase, and CINAHL databases from 2005 to 2020. Search Strategy: Guided by the lactation conceptual model, the authors searched for peer-reviewed studies with terms related to milk volume, pump dependency, critically ill infants, and modifiable factors, which may influence milk volume and assessed 46 eligible studies. Data Extraction: Data were extracted by 3 reviewers with a systematic staged review approach. Results: Evidence from 26 articles found expressed milk volume may be influenced by multiple potentially modifiable factors. Simultaneous expression with a hospital-grade electric pump at least 5 times per day beginning 3 to 6 hours after delivery, and adding complementary techniques including hand expression, hands-on-pumping, music, breast massage, warm compresses, skin-to-skin care, and the mother expressing near her infant may promote increased milk volume. Implications for Practice and Research: Healthcare providers should assist pump-dependent mothers with early initiation and frequent milk removal with a hospital-grade breast pump. Further research is needed to explore optimal frequency of expressions, dose and timing of skin-to-skin care, and other targeted strategies to improve expressed milk volume.
Feeding preterm infants mother’s own milk (MOM) lowers rates of sepsis, decreases necrotizing enterocolitis, and shortens hospital stay. In the absence of freshly expressed MOM, frozen MOM (FMOM) is provided. When MOM is unavailable, preterm infants are often fed pasteurized donor human milk (DHM), rendering it devoid of beneficial bacteria. We have previously reported that when MOM is inoculated into DHM to restore the live microbiota [restored milk (RM)], a similar microbial diversity to MOM can be achieved. Yet, it is unknown if a similar diversity to MOM can be obtained when FMOM is inoculated into DHM. The goal of this study was to determine whether a similar microbial composition to MOM could be obtained when FMOM is used to personalize DHM. To this end, a fresh sample of MOM was obtained and divided into fresh and frozen fractions. MOM and FMOM were inoculated into DHM at different dilutions: MOM/FMOM 10% (RM/FRM10) and MOM/FMOM 30% (RM/FRM30) and incubated at 37°C. At different timepoints, culture-dependent and culture-independent techniques were performed. Similar microbiota expansion and alpha diversity were observed in MOM, RM10, and RM30 whether fresh or frozen milk was used as the inoculum. To evaluate if microbial expansion would result in an abnormal activation on the innate immune system, Caco-2 epithelial cells were exposed to RM/FRM to compare interleukin 8 levels with Caco-2 cells exposed to MOM or DHM. It was found that RM samples did not elicit a significant increase in IL-8 levels when compared to MOM or FMOM. These results suggest that FMOM can be used to inoculate DHM if fresh MOM is unavailable or limited in supply, allowing both fresh MOM and FMOM to be viable options in a microbial restoration strategy.
The purpose of this scoping review was to examine the oral microbiome composition in preterm infants, sampling and collection methods, as well as exposures associated with oral microbiome composition and health implications. We conducted a scoping review of the literature using the Arskey and O'Malley framework. We identified a total of 13 articles which met our inclusion criteria and purpose of this scoping review. Articles included in this review compared the oral microbiome in preterm infants to term infants, examined alterations to the oral microbiome over time, compared the oral microbiome to different body site microbiomes, and explored associations with clinically relevant covariates and outcomes. Exposures associated with the diversity and composition of the oral microbiome in preterm infants included delivery mode, oral feeding, oropharyngeal care, skin-to-skin care, and antibiotics. Day of life and birth weight were also associated with oral microbiome composition. The oral microbiome may be associated with the composition of the tracheal and gut microbiomes, likely due to their proximity. Alpha and beta diversity findings varied across studies as well as the relative abundance of taxa. This is likely due to the different sampling techniques and timing of collection, as well as the wide range of infant clinical characteristics. Multiple factors may influence the composition of the oral microbiome in preterm infants. However, given the heterogeneity of sampling techniques and results within this review, the evidence is not conclusive on the development as well as short- and long-term implications of the oral microbiome in preterm infants and needs to be explored in future research studies. Key Points
OBJECTIVES/SPECIFIC AIMS: Aim 1: To compare frozen MOM to fresh MOM over time as an agent to inoculate DHM and measure the enrichment of commensal microbes and their beneficial bioactive components similar to MOM. Hypothesis: Frozen or fresh MOM inoculated in DHM will produce similar microbial content to MOM over time allowing for the production of beneficial bacterial compounds that may contribute to host immune response. Aim 2: To determine the effect of MOM storage (fresh vs frozen) on the expansion of bioactive components from live microbiota in DHM. Hypothesis: Both fresh and frozen MOM will produce similar results when inoculated into DHM to restore the microbial content (including their bioactive components) similar to each MOM sample. Aim 3: To compare the microbiome found in a mother’s MOM to the microbiome in her infant’s stool. Hypothesis: The mother/infant pair will share a common microbiome between the mother’s MOM and her infant’s stool. METHODS/STUDY POPULATION: Subjects will include 12 pump-dependent mothers of infants born < 34 weeks gestation admitted to the University of Florida Health Shands Hospital, Neonatal Intensive Care Unit (NICU). Inclusion criteria consists of mothers expressing over 100 ml of MOM per day, producing at least 45 ml of MOM at an expression session, at least 18 years of age, and speak English. Mothers are excluded if they have taken antibiotics within 3 days of sample collection, are HIV+, or delivered an infant who has a chromosomal abnormality or is severely ill. An expressed MOM sample will be collected and divided into two fractions: (A) fresh and (B) frozen at -20C for 24 h. The fresh fraction (A) will be processed immediately while the frozen fraction (B) will be processed after 24 h. Each MOM will be inoculated in DHM at dilutions of 10% and 30% and incubated at different time points: 0 h (T0), 2 h (T2), 4 h (T4) at 37°C. At each time point, total viable cell counts as well as microbiome analysis through 16S ribosomal shotgun sequencing will be performed and compared for differences. Bacteria isolated from each MOM will be saved, identified through 16S ribosomal sequencing and grown in culture for future studies. Fecal samples from each corresponding infant will be collected within 48 h after collection of the MOM sample. Stools will be homogenized and subjected to DNA extraction to perform 16S ribosomal shotgun sequencing. Microbiome analysis will be conducted, compared between fecal samples as well as with the microbiome of the MOM. RESULTS/ANTICIPATED RESULTS: Study is ongoing. We anticipate similar results with fresh or frozen MOM to that of a previous pilot study, where enriched microbiota similar to MOM was found when fresh MOM was inoculated and incubated in DHM. The microbiome analysis of the infant fecal samples may illustrate the influence that the microbiome of the MOM may have on the development of the infants’ gastrointestinal microbiota. DISCUSSION/SIGNIFICANCE OF IMPACT: The purpose of this study is to provide evidence on the ability, timing, and efficacy of inoculating DHM with fresh and frozen MOM. Study results will inform future studies to support the implementation of an inoculation procedural protocol to be used in clinical practice and human milk banking. The description of the MOM microbiome, as well as the gastrointestinal microbiome, will expand scientific knowledge on the role breast milk has on the origins of health and disease.
