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.

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..

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.

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.

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?

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.

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.

Mother's Own Milk Feeding and Severity of Respiratory Illness in Acutely Ill Children: An Integrative Review.

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.

Correction: Mediators of racial and ethnic disparity in mother's own milk feeding in very low birth weight infants.

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

Infant, Maternal, and Neighborhood Predictors of Maternal Psychological Distress at Birth and Over Very Low Birth Weight Infants' First Year of Life.

OBJECTIVE: To use a social-ecological conceptualization to analyze change of maternal distress, defined as depression, anxiety, and perinatal-specific post-traumatic stress (PPTS), across very low birth weight (VLBW) infants' first year of life and to identify infant, maternal, and neighborhood predictors of these changes over time. METHODS: Mothers of VLBW infants (n = 69) completed psychological distress questionnaires 2 to 4 weeks after infant birth, 2 weeks before infant discharge from neonatal intensive care unit, and at infants' 4- and 8-month corrected age (age adjusted for prematurity). Infant and maternal sociodemographic data were collected from medical chart review. Neighborhood data were obtained through US census data. Multilevel linear growth modeling was used to (1) predict unstandardized estimates of mothers' initial levels of depression, anxiety, and PPTS at the time of infant's birth and the rate of change of these markers of distress over time and (2) model unstandardized estimates of infant, maternal, and neighborhood as predictors of distress at infants' birth and change over time. RESULTS: Unstandardized estimates from multilevel linear growth modeling revealed depression (-2.8), anxiety (-1.4), and PPTS (-0.7) declined over infants' first year of life (<0.001). Mothers residing in lower-income homes and neighborhoods, respectively, reported lower anxiety (-11.2, p = 0.03) and PPTS (-31.1, p = 0.01) at infant birth. Greater infant birth weight predicted both lower anxiety (-0.02, p = 0.02) and lower PPTS (-0.02, p = 0.005). CONCLUSION: Mothers psychologically recover over VLBW infants' first year of life. Results add to a building literature about socioeconomically disadvantaged mothers of preterm infants, reporting lower distress; this warrants additional research.

Priorities for Contraception and Lactation Among Breast Pump-Dependent Mothers of Premature Infants in the Neonatal Intensive Care Unit.

Objective: Determine the knowledge and priorities for postpartum contraception and lactation in mothers of premature infants. Design: Twenty-five mothers of premature infants (mean gestational age = 29.9 weeks) hospitalized in a tertiary neonatal intensive care unit (NICU) participated in a multi-methods study using a multiple-choice contraceptive survey and qualitative interview in the first 2 weeks postpartum. Data were analyzed using content analysis and descriptive statistics. Results: Although 60% of mothers planned to use contraception, all questioned the timing of postpartum contraceptive counseling while recovering from a traumatic birth and coping with the critical health status of the infant. All mothers prioritized providing mothers' own milk (MOM) over the use of early hormonal contraception because they did not want to "take any risks" with their milk. They had limited knowledge of risks for repeat preterm birth (e.g., prior preterm birth: n = 13, 52%; multiple birth: n = 9, 36%; no knowledge: n = 3, 12%); only two mothers (0.08%) were counseled about the risks of a short interpregnancy interval. Conclusion: The context of the infants' NICU admission and the mother's desire to "do what is best for the baby" by prioritizing MOM should be integrated into postpartum contraceptive counseling for this population.

Human Milk and Clinical Outcomes in Preterm Infants.

The LOVE MOM cohort (Longitudinal Outcomes of VLBW Infants Exposed to Mothers' Own Milk; NIH: R010009; Meier PI) enrolled 430 infants with very low birth weight (VLBW) between 2008 and 2012 to study the impact of the dose and exposure period of MOM during hospitalization in the neonatal intensive care unit (NICU) on potentially preventable complications of prematurity and their associated costs. In this prospective study, MOM and formula feedings were calculated daily (mL), medical diagnoses for NICU morbidities (necrotizing enterocolitis [NEC], late-onset sepsis [sepsis], and bronchopulmonary dysplasia [BPD]) were confirmed independently by 2 neonatologists, and propensity scoring was used to analyze covariates. Neurodevelopmental outcome was measured for a subset of 251 LOVE MOM infants at 20 months of age, corrected for prematurity (CA). Data revealed a dose-response relationship between higher amounts of MOM received during critical NICU exposure periods and a reduction in the risk of NEC, sepsis, BPD, and their costs, as well as higher cognitive index scores at 20 months CA. MOM appears to function via different mechanisms during NICU exposure periods to reduce the risk of potentially preventable complications and their costs in VLBW infants. Institutions should prioritize the economic investments needed to acquire, store, and feed high-dose MOM in this population.

Mediators of racial and ethnic disparity in mother's own milk feeding in very low birth weight infants.

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.