Biomarker-based text messages to promote lactation success in mothers of critically Ill infants: a randomized controlled pilot study.

OBJECTIVE: Infrequent breast pumping limits mother's own milk production in mothers of infants admitted to the neonatal intensive care unit. We aimed to determine the feasibility and benefit of biomarker-based personalized text messages on pumping frequency and milk sodium levels. A secondary aim examined lactation outcomes. STUDY DESIGN: In this randomized controlled pilot study, 51 mothers were randomized to receive personalized text messages regarding pumping frequency or standard care. RESULTS: There were no differences in pumped milk volume or sodium level, however, there was a trend towards the intervention group pumping more frequently, which was significant on day 5 (p = 0.035), and they lactated nearly 9 days longer. Post-hoc analysis found the intervention group tended to be more likely to pump ≥ 500 mL by day14 (p = 0.08), a marker of long-term lactation success. CONCLUSION: Personalized biomarker-based text messages are feasible and may support lactation in mothers of critically ill infants.

A systematic review of contaminants in donor human milk.

Donor human milk (DHM) from a milk bank is the recommended feeding method for preterm infants when the mother's own milk (MOM) is not available. Despite this recommendation, information on the possible contamination of donor human milk and its impact on infant health outcomes is poorly characterised. The aim of this systematic review is to assess contaminants present in DHM samples that preterm and critically ill infants consume. The data sources used include PubMed, EMBASE, CINAHL and Web of Science. A search of the data sources targeting DHM and its potential contaminants yielded 426 publications. Two reviewers (S. T. and D. L.) conducted title/abstract screening through Covidence software, and predetermined inclusion/exclusion criteria yielded 26 manuscripts. Contaminant types (bacterial, chemical, fungal, viral) and study details (e.g., type of bacteria identified, study setting) were extracted from each included study during full-text review. Primary contaminants in donor human milk included bacterial species and environmental pollutants. We found that bacterial contaminants were identified in 100% of the papers in which bacterial contamination was sought (16 papers) and 61.5% of the full data set (26 papers), with the most frequently identified genera being Staphylococcus (e.g., Staphylococcus aureus and coagulase-negative Staphylococcus) and Bacillus (e.g., Bacillus cereus). Chemical pollutants were discovered in 100% of the papers in which chemical contamination was sought (eight papers) and 30.8% of the full data set (26 papers). The most frequently identified chemical pollutants included perfluoroalkyl substances (six papers), toxic metal (one paper) and caffeine (one paper). Viral and fungal contamination were identified in one paper each. Our results highlight the importance of establishing standardisation in assessing DHM contamination and future studies are needed to clarify the impact of DHM contaminants on health outcomes.

Leveraging mHealth and a milk expression frequency biomarker during postpartum to prolong lactation among parents of critically ill infants: a pilot study.

OBJECTIVE: To assess the feasibility and potential benefits of personalized biomarker-based text messages in prolonging lactation among parents of critically ill infants. STUDY DESIGN: Thirty-six participants were randomized to receive either daily texts with Mother's Own Milk (MOM) sodium levels or standard care. Surveys at months 1 and 3 assessed whether infants were receiving exclusive MOM feeding, any MOM feeding, and whether the parent was still lactating. Kaplan-Meier and log-rank tests were used for time-to-event analysis within and between intervention and control groups. RESULTS: Participants were predominantly on Medicaid (72%), delivered infants <1500 g, and by c-section (56%). Kaplan-Meier probabilities at month 3 suggest prolonged MOM feeding (63% [0.95CI, 0.43-0.91] vs. 41% [0.95CI, 0.21-0.67]) and lactation (63% [0.95CI, 0.42-0.95] vs. 37% [0.95CI, 0.18-0.76]) in the enhanced group compared to the control group. CONCLUSION: Personalized biomarker-based text messages are feasible and may prolong lactation and MOM feeding among parents of critically ill infants.

Antepartum Breast Pump Education for Mothers and Their Support Person: Effect on Time to First Expression and Lactation Outcomes-A Randomized Controlled Pilot Study.

Objective: To determine the effect of providing antenatal education regarding milk expression to the support person (SP) of mothers of preterm infants on time to initial milk expression following delivery and daily volume of expressed mother's own milk. Methods: Sixty-one mothers delivering infants <35 weeks gestation and their SP were randomized to receive antenatal education regarding milk expression or to receive standard care. Time to initiation of milk expression was determined through self-report and verified through the electronic medical records. Expressed milk volume was measured on days 1-7 and weekly for 3 weeks. Results: No difference in time to first expression or expressed milk volume was found between groups. Posthoc analysis suggests those in the antenatal education group were more likely to express without nursing assistance and expressed more frequently during days 1-5. Conclusions: SP antenatal education may be an important step in supporting lactation in mothers of critically ill infants. Further research is needed to determine whether SP education during both the antenatal and early postpartum periods could improve lactation success. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04006509.

Effect of Postpartum Depo Medroxyprogesterone Acetate on Lactation in Mothers of Very Low-Birth-Weight Infants.

Objective: This study examined the effect of postpartum administration of depo medroxyprogesterone acetate (DMPA) on milk production, time to onset of secretory activation, lactation duration, and infant consumption of mother's own milk (MOM) in mothers of preterm very low-birth-weight (VLBW) infants. Materials and Methods: We conducted a secondary analysis of data from mothers who delivered infants weighing ≤1,500 g and at ≤32 weeks' gestation. The volume of milk produced was measured on days 1-7, 14, and 21 by weighing all expressed milk on an electronic scale. Time to secretory activation was determined through self-report of a feeling of breast fullness. Information on lactation duration and the percent of feeds consisting of MOM consumed by infants was obtained from the medical records. Results: Mothers who received postpartum DMPA were more likely to be African American (72.4% versus 31.4%; p = 0.0006), unemployed (65.5% versus 44.5%; p = 0.027), and Medicaid eligible (89.7% versus 67.2%; p = 0.019). There were no differences in daily milk production between mothers who received DMPA before hospital discharge (n = 29) compared with those who did not (n = 141). When mothers who reached secretory activation before receiving DMPA were removed from analysis, receiving DMPA was associated with a later onset of secretory activation (103.7 versus 88.6 hours; p = 0.028). There were no statistically significant differences between the study groups in lactation duration or infant MOM consumption. Conclusions: DMPA, when administered postpartum to mothers of preterm VLBW infants, delayed secretory activation, but had no detrimental effect on milk production or lactation duration. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01892085.

Measures of Lactation Outcomes in Women Delivering Preterm Infants.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: Measures of lactation outcomes were reviewed and synthesized. Insights on best practices and future research directions are provided. RESULTS: 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. DISCUSSION: 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.

Demographic, Social, and Personal Factors Associated With Lactation Cessation by 6 Weeks in Mothers of Very Low Birth Weight Infants.

BACKGROUND: Although mother's own milk decreases prematurity-associated morbidities, mothers of infants born preterm and very low birth weight experience a significantly shorter lactation duration. Little is known regarding factors associated with lactation cessation during the hospitalization of a very low birth weight infant. RESEARCH AIM: To determine demographic, social, and personal factors associated with lactation cessation by 6-weeks postpartum in mothers delivering very low birth weight infants. METHODS: We used a retrospective, longitudinal, two-group comparison design using data from a randomized control study. Mothers of very low birth weight infants (N = 142) were enrolled from a labor and delivery unit associated with a Level 4 neonatal intensive care unit. Demographic, social, and health information was obtained from the medical records. Participants were surveyed regarding lactation goals, experience, and reason(s) for cessation. RESULTS: Participants who did not continue lactating for more than 6 weeks were more likely to be unemployed (p = .019), Medicaid eligible (p = .009), less educated (p < .031), smoke (p = .002), provide less skin-to-skin care (p = .007), and to delay the decision to provide their milk to their infant (p = .007). After Bonferroni adjustment, only minutes of skin-to-skin care remained statistically significant. Insufficient maternal milk production was the most common reason for lactation cessation. CONCLUSION: While the etiology of lactation cessation is often non-modifiable, strategies aimed at maintaining mother's own milk production, smoking cessation, increasing skin-to-skin care, and promoting an earlier decision to lactate, may prolong lactation duration in this vulnerable population.This RCT was registered (2012-00071) with ClinicalTrials.com on 6/28/2013.

Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants.

BACKGROUND: Inconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants. RESEARCH AIMS: To compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production. METHODS: Indicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1-7 and then weekly for 6 weeks. RESULTS: In 69 mothers of infants born ≤ 32 weeks' gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1-7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 (p = .028 and .011), those with only normal lactose levels produced more on Day 42 (p = .026) and those with only normal sodium levels on Day 28 (p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2-5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2-5 (all p < .020). CONCLUSION: Mothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.

Optimization of Molecular Dynamics Simulations of c-MYC1-88-An Intrinsically Disordered System.

Many of the proteins involved in key cellular regulatory events contain extensive intrinsically disordered regions that are not readily amenable to conventional structure/function dissection. The oncoprotein c-MYC plays a key role in controlling cell proliferation and apoptosis and more than 70% of the primary sequence is disordered. Computational approaches that shed light on the range of secondary and tertiary structural conformations therefore provide the only realistic chance to study such proteins. Here, we describe the results of several tests of force fields and water models employed in molecular dynamics simulations for the N-terminal 88 amino acids of c-MYC. Comparisons of the simulation data with experimental secondary structure assignments obtained by NMR establish a particular implicit solvation approach as highly congruent. The results provide insights into the structural dynamics of c-MYC1-88, which will be useful for guiding future experimental approaches. The protocols for trajectory analysis described here will be applicable for the analysis of a variety of computational simulations of intrinsically disordered proteins.

Timing of milk expression following delivery in mothers delivering preterm very low birth weight infants: a randomized trial.

OBJECTIVE: To determine the effect of timing of expression initiation on mother's own milk production and time to secretory activation in mothers of preterm infants. STUDY DESIGN: 180 mothers delivering infants ≤1500 grams and ≤32 weeks gestation were randomized to begin expression within 60 (early), 61-180 (intermediate) or 181-360 (late) minutes following delivery. Milk volume was measured on days 1-7 and weekly for 6 weeks. Time to secretory activation was determined through self-report. RESULTS: The late group produced more milk than the early group in the first 3 days (p = 0.015-0.031) and over 6 weeks (p = 0.045). The late group had more expressions on day 1 (early: p = 0.049; intermediate; p = 0.048). CONCLUSION: Initiation of expression at 181-360 min following delivery was associated with increased milk production for 6 weeks following delivery. Further research is needed to determine the effect of expression frequency on milk production in the first days following birth.

Factors Associated with Re-Enrollment of Patients from a Specialist Community Palliative Care Service.

Objective: The aim of this study was to describe the patterns of discharge and re-enrollment to a community palliative care service, and to identify factors associated with re-enrollment. Background: Community-based palliative care is a limited resource. The evidence base to guide discharge practices from community palliative care services is limited. Methods: A retrospective audit of the electronic medical records for all patients discharged from the Sacred Heart Community Palliative Care Service (SHCPCS), Sydney, from July 2010 to July 2016 was conducted. Patients were excluded if they were discharged due to death, transferred out of catchment area, declined the service, transferred to another hospital, or were referred inappropriately. Data extracted included sociodemographic variables, living situation, diagnoses, and discharge and re-enrollment details. Using binary logistic regression analysis, predictive factors, including socio-demographic characteristics, diagnosis and length of episode of care, were evaluated. Results: Of the 739 patients who met the inclusion criteria, 42 (5.7%) were re-enrolled to the service. The median length of the initial episode of care was 65 days and the median timeframe between discharge and re-enrollment was 216 days. Patients living in residential care facilities (odds ratio [OR] 3.45; 95% confidence interval [CI] 1.28-9.28; p = 0.01) and those with malignant diagnoses (OR 2.22; 95% CI 1.00-4.93; p = 0.04) had higher rates of re-enrollment. Discussion: The proportion of patients re-enrolled to the service was low. Both patient factors and disease factors were associated with re-enrollment. Future prospective studies evaluating prognostic factors to assist with effective discharge processes and guidelines are warranted.

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.

Strategies to increase milk volume in mothers of VLBW infants.

The provision of breast milk to premature VLBW infants is associated with significant health benefits. Unfortunately, the delivery of breast milk to these vulnerable infants is often limited due to insufficient maternal milk supply. Several interventions have been investigated with respect to increasing milk volume in mothers of VLBW infants but confusion exists concerning the interventions' effectiveness. The purpose of this systematic review is to critique the evidence regarding specific milk expression strategies that aim to improve milk volume in mothers of VLBW infants.Published article references, electronic databases, dissertations and theses, and select conference proceedings were searched with the goal of finding studies that target VLBW infants and milk expression techniques in which breast milk volume was an outcome. Analysis of evidence revealed an association between increased milk volume and early initiation of expression, increased frequency of expression, and provision of kangaroo care. The use of simultaneous or sequential milk expression and duration of milk expression sessions were not found to significantly improve milk volume. These results may be used to formulate specific strategies designed to increase breast milk volume in this population.

Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants.

OBJECTIVE: To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. STUDY DESIGN: Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). RESULTS: Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. CONCLUSIONS: In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit.

The association of maternal pre-pregnancy body mass index with breastfeeding initiation.

Recent evidence extends the health benefits of breastfeeding to include reduction of maternal body mass index (BMI) and childhood obesity. Since most women decide if they will breastfeed prior to pregnancy, it is important to understand, given the high population prevalence of obesity, if maternal underweight, overweight or obese status is associated with breastfeeding initiation. Population-based study. Florida resident birth certificate records. All live singleton births (2004-2009), excluding observations that lacked the primary outcomes of maternal pre-pregnancy BMI and breastfeeding initiation (final sample of 1,161,949 unique observations). Odds of initiating breastfeeding, adjusted by maternal and infant factors, stratified by pre-pregnancy BMI, categorized as underweight, normal, overweight and obese. Adjusting for the known maternal factors associated with breastfeeding initiation, underweight and obese women were significantly less likely to initiate breastfeeding than women with normal BMI, (adjusted odds ratio 0.87, 95 % confidence interval 0.85-0.89 for underweight women; 0.84, 95 % CI 0.83-0.85 for obese women). The magnitude of these findings did not significantly vary by race or ethnicity. Medicaid status and adherence to the Institute of Medicine's 2009 pregnancy weight gain recommendations had only minor influences on breastfeeding initiation. Among adolescents, only underweight status predicted breastfeeding initiation; obesity did not. Underweight and obese women have significantly lower rates of breastfeeding initiation compared to women with normal pre-pregnancy BMI. Future studies need to address the health care, social, and physical barriers that interfere with breastfeeding initiation, especially in underweight and obese women, regardless of race, ethnicity or income.

Effect of breast milk on hospital costs and length of stay among very low-birth-weight infants in the NICU.

PURPOSE: Care of the very low-birth-weight (VLBW) infant is associated with prolonged hospitalization and increased hospital costs. Specific complications of prematurity, including necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and feeding intolerance, contribute to increased cost and length of hospitalization in this population. The provision of breast milk to VLBW infants has been associated with decreased incidence of NEC and LOS as well as fewer days required to achieve full enteral feedings. The purpose of this study was to determine the impact of breast milk on length of hospitalization and hospital costs among VLBW infants in the neonatal intensive care unit (NICU). SUBJECTS: A total of 80 infants weighing less than 1500 g, born prior to 32 weeks' gestation and who remained in the home hospital until discharge. DESIGN: This descriptive comparative study examined cost of hospitalization and length of stay between 2 groups of VLBW premature infants fed either exclusively formula (n = 40) or at least 50% breast milk (n = 40) during their hospitalization. METHODS: A retrospective chart review was used to collect information concerning patient demographics, discharge information, and nutritional variables. Information regarding hospital costs was obtained from the hospital's patient accounting office. MAIN OUTCOME MEASURES: Independent t tests were used to compare demographic data, length of hospitalization, and cost of care between the 2 groups. PRINCIPAL RESULTS: No statistically significant differences in length of stay or cost of care were found between infants fed at least 50% breast milk and those who were exclusively formula fed. Descriptive data concerning length of stay and cost of care for VLBW infants and those infants weighing less than 1000 g are presented. CONCLUSION: This article presents a descriptive comparative study on the effect of providing at least 50% breast milk feedings compared with formula feeding on days to discharge and cost of hospitalization in VLBW infants in the NICU. It also provides information concerning cost of care and length of stay in VLBW and infants weighing less than 1000 g.

Ankyloglossia, exclusive breastfeeding, and failure to thrive.

A 6-month-old term boy was hospitalized to evaluate the cause of his failure to thrive, mandated as part of an investigation by the Department of Children and Families after an allegation of medical neglect was made. On admission the patient was below birth weight, and a medical workup for failure to thrive was pursued; however, he was noted to have severe ankyloglossia and was an exclusively breastfed infant. The only interventions during his hospitalization were frenotomy and assistance to the mother to increase her milk supply. The infant immediately experienced weight gain and has continued to show slow, but steady, weight gain as an outpatient. We illustrate here many of the controversies concerning ankyloglossia.

Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD).

PURPOSE: The pharmacokinetic profile of pantoprazole granules was assessed in neonates and preterm infants with gastroesophageal reflux disease (GERD) in a multicenter, randomized, open-label trial. METHODS: Patients were randomly assigned to either the pantoprazole 1.25 mg (approx. 0.6 mg/kg) or 2.5 mg (approx. 1.2-mg/kg) group and treated for > or =5 consecutive days. Blood was sampled either at 0, 2, 8, and 18 h postdose or at 0, 1, 4, and 12 h postdose on day 1 and at 3 and 6 h postdose after > or =5 consecutive doses. Cytochrome P450 2C19 (CYP2C19) and CYP3A4 genotypes were determined. Safety was monitored. Population pharmacokinetics (popPK) analyses were conducted using nonlinear mixed-effects modeling. RESULTS: The popPK modeling of the pantoprazole 1.25 mg and 2.5 mg groups obtained mean (+/-standard deviation) estimates for the area under the plasma concentration versus time curve (AUC) of 3.54 (+/-2.82) and 7.27 (+/-5.30) microg h/mL, respectively, and mean estimates for half-life of 3.1 (+/-1.5) and 2.7 (+/-1.1) h, respectively. Pantoprazole did not accumulate following multiple-dose administration. The two patients with the CYP2C19 poor metabolizer genotype had a substantially higher AUC than extensive metabolizers. No safety-related discontinuations occurred. CONCLUSIONS: In preterm infants and neonates, pantoprazole granules were generally well tolerated, mean exposures with pantoprazole 2.5 mg were slightly higher than that in adults who received 40 mg. While the half-life was longer, accumulation did not occur.