Loss of miR-101-3p in melanoma stabilizes genomic integrity, leading to cell death prevention.

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.

Where does the time go? Temporal patterns of pumping behaviors in mothers of very preterm infants vary by sociodemographic and clinical factors.

Background: Mothers of very preterm (<32 weeks gestational age [GA]) infants are breast pump dependent and have shorter duration of milk provision than mothers of term infants. The opportunity (i.e., time) cost of pumping and transporting mother's own milk (MOM) from home to the NICU may be a barrier. There is a paucity of data regarding how much time mothers actually spend pumping. Objective: To investigate the variation in pumping behavior by postpartum week, maternal characteristics, and infant GA. Methods: Prospectively collected pump log data from mothers enrolled in ReDiMOM (Reducing Disparity in Mother's Own Milk) randomized, controlled trial included pumping date and start time and end time of each pumping session for the first 10 weeks postpartum or until the infant was discharged from the NICU, whichever occurred first. Outcomes included number of daily pumping sessions, number of minutes spent pumping per day, and pumping behaviors during 24-h periods, aggregated to the postpartum week. Medians (interquartile ranges) were used to describe outcomes overall, and by maternal characteristics and infant GA. Results: Data included 13,994 pump sessions from 75 mothers. Maternal characteristics included 55% Black, 35% Hispanic, and 11% White and 44% <30 years old. The majority (56%) of infants were born at GA 28-31 weeks. Mothers pumped an average of less than 4 times per day, peaking in postpartum week 2. After accounting for mothers who stopped pumping, there was a gradual decrease in daily pumping minutes between postpartum weeks 2 (89 min) and 10 (46 min). Black mothers pumped fewer times daily than non-Black mothers after the first 2 weeks postpartum. Conclusion: On average mothers pumped less intensively than the minimum recommendation of 8 times and 100 min per day. However, these pumping behaviors represent significant maternal opportunity costs that should be valued by the institution and society at large.

Milk Biomarkers of Secretory Activation in Breast Pump-Dependent Mothers of Preterm Infants: An Integrative Review.

Background: Lack of mother's own milk (MOM) at discharge from the neonatal intensive care unit (NICU) is a global problem and is often attributable to inadequate MOM volume. Evidence suggests that the origins of this problem are during the first 14 days postpartum, a time period that includes secretory activation (SA; lactogenesis II, milk coming in). Objectives: To describe and summarize evidence regarding use of MOM biomarkers (MBMs) as a measure of SA in pump-dependent mothers of preterm infants in the NICU and to identify knowledge gaps requiring further investigation. Methods: An integrative review was conducted using Whittemore and Knafl methodology incorporating the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. A search using electronic databases MEDLINE (through PubMed) and CINAHL (Cumulative Index to Nursing and Allied Health Literature) and reference lists of included articles was conducted. Results: Of the 40 articles retrieved, 6 met the criteria for inclusion. Results revealed the following five findings: (1) Achievement of SA defined by MBMs is delayed and/or impaired in mothers of preterm infants. (2) MBMs are associated with pumped MOM volume. (3) Achievement of SA defined by MBMs is associated with pumping frequency. (4) Delayed and/or impaired achievement of SA defined by MBMs may be exacerbated by maternal comorbidities. (5) There is a lack of consensus as to which MBM(s) and analysis techniques should be used in research and practice. Conclusions: MBMs hold tremendous potential to document and monitor achievement of SA in mothers of preterm infants, with multiple implications for research and clinical practice.

Clinically Integrated Breastfeeding Peer Counseling to Promote Breastfeeding Equity.

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..

Infant factors that impact the ecology of human milk secretion and composition-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 3.

Infants drive many lactation processes and contribute to the changing composition of human milk through multiple mechanisms. This review addresses the major topics of milk removal; chemosensory ecology for the parent-infant dyad; the infant's inputs into the composition of the human milk microbiome; and the impact of disruptions in gestation on the ecology of fetal and infant phenotypes, milk composition, and lactation. Milk removal, which is essential for adequate infant intake and continued milk synthesis through multiple hormonal and autocrine/paracrine mechanisms, should be effective, efficient, and comfortable for both the lactating parent and the infant. All 3 components should be included in the evaluation of milk removal. Breastmilk "bridges" flavor experiences in utero with postweaning foods, and the flavors become familiar and preferred. Infants can detect flavor changes in human milk resulting from parental lifestyle choices, including recreational drug use, and early experiences with the sensory properties of these recreational drugs impact subsequent behavioral responses. Interactions between the infant's own developing microbiome, that of the milk, and the multiple environmental factors that are drivers-both modifiable and nonmodifiable-in the microbial ecology of human milk are explored. Disruptions in gestation, especially preterm birth and fetal growth restriction or excess, impact the milk composition and lactation processes such as the timing of secretory activation, adequacy of milk volume and milk removal, and duration of lactation. Research gaps are identified in each of these areas. To assure a sustained and robust breastfeeding ecology, these myriad infant inputs must be systematically considered.

The Role of Work as a Social Determinant of Health in Mother's Own Milk Feeding Decisions for Preterm Infants: A State of the Science Review.

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

More evidence: Mothers' own milk is personalized medicine for very low birthweight infants.

"Human milk sources and fortification: Impact on fecal microbiota and calprotectin in premature infants" highlights improved outcomes in predominantly mothers' own milk-fed versus predominantly pasteurized donor human milk-fed VLBW infants, regardless of fortifier type. Research and practice implications are reviewed.

Cost Savings of Mother's Own Milk for Very Low Birth Weight Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: The study aim was to determine the relationship between hospitalization costs and mother's own milk (MOM) dose for very low birth weight (VLBW; < 1500 g) infants during the initial neonatal intensive care unit (NICU) stay. Additionally, because MOM intake during the NICU hospitalization is associated with a reduction in the risk of late-onset sepsis, necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD), we aimed to quantify the incremental cost of these potentially preventable complications of prematurity. METHODS: The study included 430 VLBW infants enrolled in the Longitudinal Outcomes of Very Low Birthweight Infants Exposed to Mothers' Own Milk prospective cohort study between 2008 and 2012 at Rush University Medical Center in Chicago, IL, USA. NICU hospitalization costs included hospital, feeding, and physician costs. The average marginal effect of MOM dose and prematurity-related complications known to be reduced by MOM intake on NICU hospitalization costs were estimated using generalized linear regression. RESULTS: The mean NICU hospitalization cost was $190,586 (standard deviation $119,235). The marginal cost of sepsis was $27,890 (95% confidence interval [CI] $2934-$52,646), of NEC was $46,103 (95% CI $16,829-$75,377), and of BPD was $41,976 (95% CI $24,660-59,292). The cumulative proportion of MOM during the NICU hospitalization was not significantly associated with cost. CONCLUSIONS: A reduction in the incidence of complications that are potentially preventable with MOM intake has significant cost implications. Hospitals should prioritize investments in initiatives to support MOM feedings in the NICU.

Study protocol for reducing disparity in receipt of mother's own milk in very low birth weight infants (ReDiMOM): a randomized trial to improve adherence to sustained maternal breast pump use.

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.

Neurodevelopmental Outcome in Very Low Birth Weight Infants Exposed to Donor Milk.

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..

Prepregnancy Body Mass Index Is Associated with Time-Dependent Changes in Secretory Activation Measures During the First 7 Days Postpartum in Breast Pump-dependent Mothers of Premature Infants.

Background: Little is known about the biology of secretory activation (SA) in overweight and obese (OW/OB) mothers who are breast pump dependent with a premature infant in the neonatal intensive care unit. Objective: To compare time-dependent changes in daily pumped milk volume, maternal milk sodium (Na) concentration, and Na-to-potassium (K) ratios (Na:K) in the first 14 days postpartum in breast pump-dependent mothers with prepregnancy body mass index (BMI) <27 and BMI ≥27 kg/m2. Design/Methods: This secondary analysis for 39 subjects, 44% (n = 17) with prepregnancy BMI <27 and 56% (n = 22) with BMI ≥27, included transformed data of outcome measures, chi-square, t-tests, and growth curve models. Results: For days 1-7, daily pumped milk volume increased significantly more rapidly for mothers with BMI <27 (65.82 mL/d) versus BMI ≥27 (33.08 mL/d), but the daily rate of change in pumped milk volume during days 8-14 was not statistically different. Daily milk Na concentration decreased significantly faster in BMI <27 (-3.93 mM/d) versus BMI ≥27 (-2.00 mM/day) during days 1-7, but was not significantly different for days 8-14. No statistical differences were noted for Na:K ratio for either time period. Conclusion: These data add biologic evidence to previous research, suggesting delayed or impaired SA in OW/OB mothers, and suggest that the window of opportunity for research and clinical interventions is days 1-7 postpartum in this population.

Are Mothers Certain About Their Perceptions of Recalled Infant Feeding History?

INTRODUCTION: Maternal recall of infant feeding, a potential measurement bias, is used to identify the relationship between mothers' own milk (MOM) feeding and subsequent health outcomes. This study describes maternal recall certainty of MOM feedings at four time periods. METHOD: In this secondary analysis, mothers of children ages 4-36 months describe infants' MOM feeding and rate certainty of their recall. RESULTS: MOM was the first feeding for 78.5% of infants and received by 83% the first week, 85% the first month, and 62% the fourth month. Ratings of recall certainty were > 95% for each time period. Recall certainty was significantly different for four time periods (χ2 = 9.67, p = 0.02), with no two periods significantly different in post hoc analyses. DISCUSSION: Maternal recall certainty of infant feeding was high regardless of elapsed time. Measuring maternal recall certainty may be useful in clinical practice and studies linking MOM exposure to subsequent health outcomes.

The Interaction of Donor Human Milk Availability and Race/Ethnicity on Provision of Mother's Own Milk for Very Low Birth Weight Infants.

Objective: To compare (1) differences in mother's own milk (MOM) provision and enteral feeding outcomes, (2) differences in preterm formula and donor human milk (DHM) uses as bridges to exclusive MOM feedings at discharge, and (3) MOM and enteral feeding outcomes for racial/ethnic subgroups before and after the implementation of a hospital DHM feeding program. Methods: Retrospective data from 313 very low birth weight (VLBW; birth weight <1,500 g) infants born between January 2011 to December 2012 (pre-DHM, n = 157) and April 2013 to March 2015 (DHM, n = 156) were analyzed. Results: For this predominantly low-income and minority VLBW infant cohort, the percent of enteral fed hospitalization days was higher in the DHM group (pre-DHM 94% [88, 97] versus DHM 98% [95, 99], p < 0.001). Although MOM remained the predominant first enteral feeding type, significantly fewer DHM infants received MOM (pre-DHM 89% versus DHM 75%, p = 0.001). During days of life 1-14, a lower percentage of DHM infants received 100% MOM (pre-DHM 68% versus DHM 55%, p = 0.02). For the entire cohort, the risk for MOM discontinuation was significantly associated with maternal young age, multiparity, non-Hispanic Black race/ethnicity, and low income. Implementation of a DHM program did not predict duration of MOM feedings. However, non-Hispanic White infants had a longer duration of MOM feedings with DHM availability. Conclusions: Our findings highlight the importance of using precise dose and exposure period methodology to determine the impact of DHM on MOM provision. In addition, DHM availability may be associated with varying effects on MOM provision among racial/ethnic groups.

Racial and socioeconomic disparities in breast milk feedings in US neonatal intensive care units.

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?

Mother's Own Milk Biomarkers Predict Coming to Volume in Pump-Dependent Mothers of Preterm Infants.

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.

Strategies to increase the use of mother's own milk for infants at risk of necrotizing enterocolitis.

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.

The Economic Impact of Donor Milk in the Neonatal Intensive Care Unit.

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.

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study.

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.

Measures of Secretory Activation for Research and Practice: An Integrative Review.

Background: Maternal concern about inadequate milk volume commonly emerges in the first 2 weeks postpartum, a critical lactation period that includes secretory activation. This review summarizes the biology of secretory activation and evaluates the accuracy and feasibility of published measures of secretory activation. Materials and Methods: A systematic search of measures of secretory activation for mothers of healthy term and preterm infants yielded 62 abstracts. Following additional screening, 15 publications qualified for quantitative synthesis review and were evaluated with respect to accuracy (validated with another measure of secretory activation in the same mother) and feasibility (accessibility, cost, and ease of use). Results:Maternal perception of milk coming in (MP) is the most feasible measure, but its accuracy has not been established. Patterns of increase in maternal milk volume have been validated with maternal milk-borne biomarkers in breastfeeding, and breast pump-dependent mothers and normal values have been published. Accuracy of serial maternal urinary lactose concentrations has not been established for secretory activation and lacks feasibility. Maternal milk biomarkers are the accurate standard to which other measures are compared but currently lack feasibility for routine use. Conclusions: Use of secretory activation measures can personalize lactation care by matching maternal risk with appropriate diagnostics. Priorities for research and practice include validation of MP as a population-based screening tool, implementation of techniques that measure patterns of increase in milk volume for moderate risk populations, and the development of milk biomarker science for point-of-care use in the most complicated lactation scenarios.