Search

Human milk (HM) exposure improves short- and long-term outcomes for infants due to a complex milieu of bioactive, stem cell, anti-inflammatory, anti-microbial, and nutritive components. Given this remarkable biologic fluid, non-nutritional utilization of HM as a targeted therapeutic is being explored in pre-clinical and clinical studies. This article describes recent research pertinent to non-nutritional uses of HM for neurologic, gastrointestinal, and infectious pathologies in neonates, as well as future directions., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Intraventricular hemorrhage (IVH) is a common cause of preterm brain injury. Fresh parent's own milk (POM) contains pluripotent stem cells (SCs) that produce neuronal cells in-vitro. The permeable neonatal blood brain barrier potentially allows SC delivery. We performed the first prospective trial (clinicaltrials.gov NCT04225286) of feasibility of intranasal POM (IPOM) in preterm infants with IVH and described SC content of POM samples., Study Design: 37 Infants (mean gestation 27.7 ± 2.6 weeks, birthweight 1030 ± 320 g) with IVH (35.1% grade IV) were recruited from two tertiary Toronto NICUs. IPOM was given ideally twice daily until 28 days of age. Tolerance and adverse reactions were collected and 162 administering providers surveyed., Results: There were no major adverse reactions. Provider surveys suggested acceptability, although potential provider and subject stress requires further study. Milk cell analysis suggests wide variability between parents., Conclusions: This phase 1 study demonstrated IPOM was tolerated and feasible in preterm infants., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Pumping studies in mothers of preterm infants are limited by self-reported pumping behaviors and non-objective measures of pumped milk volume and secretory activation (SA)., Methods: Non-randomized observational study of first 14 days postpartum in 29 mothers of preterm infants. Smart pumps measured and stored pumping behaviors and pumped milk volume. Selective ion electrodes measured sodium and sodium:potassium ratio to determine SA. Generalized estimating equations, cluster analyses and multivariate regression were used., Results: SA was delayed (median 5.8 days) and impermanent. Each additional daily pumping increased odds of SA within 2 days by 48% (p = 0.01). High-intensity pumping mothers (N = 17) had greater daily and cumulative pumped milk volume than low-intensity pumping mothers (N = 12). Pumping variables showed daily changes in the first week, then plateaued., Conclusion: The first week postpartum is critical for optimizing pumping behaviors. Accurate, objective measures of pumping behaviors, pumped milk volume and SA are a research priority., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: Intraventricular hemorrhage (IVH) is a common cause of brain injury in preterm infants. Fresh human milk (HM) contains stem cells (SCs) that could potentially be delivered via intranasal HM (IHM). In this IHM pilot study, we describe outcomes., Study Design: Infants <33 weeks gestation with IVH were given IHM until maximum 28 days of age. Short-term neurologic outcomes and follow-up testing were compared to historic HM-fed infants. Longitudinal outcomes were plotted using linear mixed models. Weighted G-computation quantified treatment effects. Propensity score models calculated inverse probability weights for IVH grade, gestational age, and sex., Result: 37 infants (35.1% grade 3-4 IVH) were compared to 191 historic controls (17.8% grade 3-4 IVH). Post-hemorrhagic ventricular dilatation was common (25.7% IHM patients). Most weighted outcomes, although not significant, favored IHM at 4-12 and 18 months corrected age., Conclusion: This phase 1 study suggests powered trials of IHM for brain injury are needed. CLINICAL TRIAL REGISTRY NAME: clinicaltrials.gov identifier NCT04225286., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Overweight/obesity (ow/ob) is increasing in prevalence in pregnant women, and it is associated with other pro-inflammatory states, such as pre-eclampsia, gestational diabetes, and preterm labor. Data are lacking if mothers experiencing inflammatory states who deliver preterm have mother's own milk (MOM) with differing inflammatory markers or pro-inflammatory fatty acid (FA) profiles., Methods: The aim was to explore associations of maternal pre- and perinatal inflammatory states with levels of inflammatory markers and/or FAs in longitudinal samples of MOM from mothers of preterm infants born <1,250 g. Inflammatory states included pre-pregnancy ow/ob, diabetes, chorioamnionitis (chorio), preterm labor (PTL), premature rupture of membranes (PROM), pre-eclampsia, and cesarian delivery. In MOM, inflammatory markers studied included c-reactive protein (CRP), free choline, IFN-Ɣ, IL-10, IL-1β, IL-1ra, IL-6, IL-8, and TNF-α, and FAs included omega-6:omega-3 ratio, arachidonic acid, docosahexaenoic acid, linoleic acid, monounsaturated FAs, and saturated FAs. The above inflammatory states were assessed individually, and the healthiest mothers (normal BMI, no chorio, and ± no pre-eclampsia) were grouped. Regression analysis tested associations at baseline (day 5) and over time using generalized estimating equations., Results: A total of 92 infants were included who were delivered to mothers (42% ow/ob) at a median gestational age of 27.7 weeks and birth weight of 850 g. MOM CRP was 116% higher (relative change 2.16) in mothers with ow/ob at baseline than others ( p  = 0.01), and lower (relative change 0.46, 0.33, respectively) in mothers in the two "healthy groups" at baseline (both p  < 0.05) than others. MOM IL-8 levels were lower with chorio and PTL at baseline. No significant associations were found for other individual or grouped inflammatory states nor for other MOM inflammatory markers nor FA profiles at baseline., Discussion: In conclusion, MOM CRP levels are positively associated with inflammatory states, such as ow/ob. Reassuringly, there was no association between FA profiles or most other inflammatory markers and maternal inflammatory states. Further studies are needed to determine potential associations or ramifications of MOM CRP in vulnerable preterm infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Landau-Crangle, O’Connor, Unger, Hopperton, Somerset, Nir and Hoban.)

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.

Background: Mother's breastmilk is the gold standard for feeding preterm infants. Preterm delivery may be precipitated by inflammatory maternal states, but little is known about milk cytokine profiles and how they correlate with markers of infant gut inflammation (i.e., stool calprotectin) in this vulnerable population., Research Aim: To assess cytokines and inflammatory markers in milk from parents of very preterm infants over time as well as correlations between milk and infant's stool calprotectin., Method: This is a secondary analysis of milk samples collected during OptiMoM, a triple-blind randomized clinical trial of infants born < 1250 g (NCT02137473). Longitudinally collected samples were analyzed for cytokines, choline, and inflammatory markers (C-reactive protein [CRP], IFN-γ, IL-10, IL-1β, IL-1ra, IL-6, IL-8, TNF-α). Infant stools were collected for longitudinal calprotectin analysis. Generalized estimating equations quantified longitudinal profiles of milk markers and stool calprotectin, their associations, and the correlation between free choline and C-reactive protein over follow-up., Result: Participants included 92 parents and infants (median weeks of gestation 27.3, median birth weight 845 g, and prevalence of male infants 45%). In all, 212 milk samples and 94 corresponding stool calprotectin levels were collected 1-11 weeks postpartum. C-reactive protein was present in much higher concentrations than other markers, and was highest in Week 1 postpartum. It decreased over time. IL-8 and free choline also changed over time while other markers did not. There was no correlation between any milk markers and stool calprotectin., Conclusion: Milk from mothers of very preterm infants has detectable inflammatory markers, some of which change over time. Research is needed to determine if infant outcomes are associated with these markers., Competing Interests: Disclosures and Conflicts of InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Refractory neonatal hypoglycemia may be treated with glucagon infusions, which have been associated with thrombocytopenia and hyponatremia. After anecdotally noting metabolic acidosis during glucagon therapy in our hospital, an outcome not previously reported in the literature, we aimed to quantify occurrence of metabolic acidosis (base excess >-6) as well as thrombocytopenia and hyponatremia during treatment with glucagon., Methods: We performed a single-centre retrospective case series. Descriptive statistics were used and subgroups compared with Chi-Square, Fisher's Exact Test, and Mann-Whitney U testing., Results: Sixty-two infants (mean birth gestational age 37.2 weeks, 64.5% male) were treated with continuous glucagon infusions for median 10 days during the study period. 41.2% were preterm, 21.0% were small for gestational age, and 30.6% were infants of diabetic mothers. Metabolic acidosis was seen in 59.6% and was more common in infants who were not born to diabetic mothers (75% versus 24% in infants of diabetic mothers, P<0.001). Infants with versus without metabolic acidosis had lower birth weights (median 2,743 g versus 3,854 g, P<0.01) and were treated with higher doses of glucagon (0.02 versus 0.01 mg/kg/h, P<0.01) for a longer duration (12.4 versus 5.9 days, P<0.01). Thrombocytopenia was diagnosed in 51.9% of patients., Conclusions: In addition to thrombocytopenia, metabolic acidosis of unclear etiology appears to be very common with glucagon infusions for neonatal hypoglycemia, especially in lower birth weight infants or those born to mothers without diabetes. Further research is needed to elucidate causation and potential mechanisms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The COVID-19 pandemic has impacted breastfeeding and lactation globally, with clinical practices implemented early in the pandemic being mostly anti-breastfeeding, e.g., separation of mothers from their infants, and not evidence based. As the pandemic has progressed, evidence has emerged reconfirming the value of human milk and the importance of protecting and supporting breastfeeding, especially the initiation of lactation. However, it is clear that COVID-19 has changed the clinical care paradigm around breastfeeding and lactation support and, as such, it is imperative that practices adapt and evolve to maintain the emphasis on lactation support. We participated in a round table conference aiming to rescue and develop protocols and practices that support breastfeeding during the COVID-19 pandemic. One key area to target will be to maximize the use of the antenatal period. The early identification of lactation risk factors together with the development of person-centered methods to deliver breastfeeding information and education to parents-to-be will be critical. In addition, the establishment of a hospital culture that values breastfeeding and prioritizes the use of human milk will be integral for the motivation of health care professionals. That culture will also support active management of the initiation of lactation and the development of a 'back-up plan' toolkit to support the mother experiencing lactation difficulties. Post-discharge support will also be crucial with the development of both in-person and virtual lactation support programs, in particular for the immediate post-discharge period to benefit mothers who experience an early discharge process. These measures will allow for a new, adapted framework of practice that acknowledges the current COVID-19 paradigm and maintains the emphasis on the need to protect and support breastfeeding and the use of human milk., Competing Interests: JG serves as member of the National Health Council and is also director of the Dutch National Human Milk Bank. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Goudoever, Spatz, Hoban, Dumitriu, Gyamfi-Bannerman, Berns, McKechnie and Davanzo.)

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/m 2 . 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.

Background: Mother's milk improves outcomes. Referral neonatal intensive care units face unique lactation challenges with maternal-infant separation and maternal pump dependency. Little is known about lactation resource allocation in this high-risk population., Research Aims: To determine differences in human milk outcomes, (1) the proportion of infants fed exclusive or any mother's milk and (2) recorded number and volume of pumped mothers' milk bottles, between two models of lactation care in a referral neonatal intensive care unit., Methods: This retrospective, longitudinal, two-group comparison study utilized medical record individual feeding data for infants admitted at ≤ Day 7 of age and milk room storage records from reactive and proactive care model time periods (April, 2017-March, 2018; May, 2018-April, 2019). The reactive care model ( n = 509 infants, 58% male, median birth weight and gestational age of 37 weeks,) involved International Board Certified Lactation Consultant referral for identified lactation problems; whereas, the proactive model ( n = 472 infants, 56% male, median birth weight and gestational age 37 weeks) increased International Board Certified Lactation Consultant staffing, who then saw all admissions. Comparisons were performed using chi square, Mann Whitney, and t- tests., Results: A proactive lactation approach was associated with an increase in the receipt of any mother's milk from 74.3% to 80.2% ( p = .03) among participants in the proactive model group. Additionally, their milk room mean monthly bottle storage increased from 5153 ( SD 788) to 6620 ( SD 1314) bottles ( p < .01)., Conclusions: In this retrospective study at a tertiary referral neonatal intensive care unit, significant improvement inhuman milk outcomes suggests that increased resources for proactive lactation care may improve mother's milk provision for a high-risk population.

Mother's own milk (MOM) feeding is a cost-effective strategy to reduce risks of comorbidities associated with prematurity and improve long-term health of infants hospitalized in the Neonatal Intensive Care Unit (NICU). Significant racial and socioeconomic disparities exist in MOM provision in the NICU, highlighting the importance of developing strategies to reduce these disparities. Mothers of infants in the NICU experience many health concerns which may negatively impact lactation physiology. Objective measures of lactation physiology are limited but may assist in identifying mothers at particular risk. Several strategies to assist mothers of hospitalized infants are essential, including maternal education, qualified lactation professionals, early and frequent milk expression with a hospital-grade double electric breast pump, and providing support for transitioning to direct breastfeeding prior to discharge from the NICU., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Background: Mother's own milk (MOM) improves in-hospital outcomes for preterm infants. If unavailable, donor milk (DM) is often substituted. It is unclear if DM vs. formula to supplement MOM is associated with improved in-hospital outcomes in term/late preterm surgical infants with gastroschisis or intestinal atresia., Methods: This retrospective study included infants born ≥33 weeks gestational age (GA) with a birth weight of >1500 g who were admitted to a quaternary neonatal intensive care unit (NICU). Using Chi square and Mann-Whitney u testing, we compared hospital outcomes (length of stay, parenteral nutrition and central line days) before and after a clinical practice change to offer DM instead of formula in this surgical population., Results: Baseline characteristics were similar between eras for the 140 infants (median GA 37 weeks). Fewer infants in DM era were receiving formula at discharge (50.0% vs. 31.4%, p = 0.03). In sub-analyses including only small bowel atresia and gastroschisis infants, the median length of stay (35 vs. 25, p < 0.01) and the central line days (28 vs. 20, p < 0.01) were lower in the DM era., Conclusion: In this retrospective study, offering DM instead of formula was associated with less formula feeding at discharge, and in infants with gastroschisis or small bowel atresia, shorter length of stay and central line days.

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.

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.

Mother's own milk (MOM) reduces the risk of morbidities in very low birth weight (VLBW) infants. When MOM is unavailable, donor breastmilk (DM) is used, with unclear impact on short- and long-term growth. This retrospective analysis compared anthropometric data at six time points from birth to 20⁻24 months corrected age in VLBW infants who received MOM supplements of preterm formula ( n = 160) versus fortified DM ( n = 161) during neonatal intensive care unit (NICU) hospitalization. The cohort was 46% female; mean birth weight and gestational age (GA) were 998 g and 27.3 weeks. Multilevel linear growth models assessed changes in growth z -scores short-term (to NICU discharge) and long-term (post-discharge), controlling for amount of DM or formula received in first 28 days of life, NICU length of stay (LOS), birth GA, and sex. Z -scores for weight and length decreased during hospitalization but increased for all parameters including head circumference post-discharge. Short-term growth was positively associated with LOS and birth GA. A higher preterm formula proportion, but not DM proportion, was associated with slower rates of decline in short-term growth trajectories, but feeding type was unrelated to long-term growth. In conclusion, controlling for total human milk fed, DM did not affect short- or long-term growth.

Background: In the treatment of phenylketonuria (PKU), there was disparity between UK dietitians regarding interpretation of how different foods should be allocated in a low phenylalanine diet (allowed without measurement, not allowed, or allowed as part of phenylalanine exchanges). This led to variable advice being given to patients., Methodology: In 2015, British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 70) were sent a multiple-choice questionnaire on the interpretation of protein from food-labels and the allocation of different foods. Based on majority responses, 16 statements were developed. Over 18-months, using Delphi methodology, these statements were systematically reviewed and refined with a facilitator recording discussion until a clear majority was attained for each statement. In Phase 2 and 3 a further 7 statements were added., Results: The statements incorporated controversial dietary topics including: a practical 'scale' for guiding calculation of protein from food-labels; a general definition for exchange-free foods; and guidance for specific foods. Responses were divided into paediatric and adult groups. Initially, there was majority consensus (≥86%) by paediatric dietitians (n = 29) for 14 of 16 statements; a further 2 structured discussions were required for 2 statements, with a final majority consensus of 72% (n = 26/36) and 64% (n = 16/25). In adult practice, 75% of dietitians agreed with all initial statements for adult patients and 40% advocated separate maternal-PKU guidelines. In Phase 2, 5 of 6 statements were agreed by ≥76% of respondents with one statement requiring a further round of discussion resulting in 2 agreed statements with a consensus of ≥71% by dietitians in both paediatric and adult practice. In Phase 3 one statement was added to elaborate further on an initial statement, and this received 94% acceptance by respondents. Statements were endorsed by the UK National Society for PKU., Conclusions: The BIMDG dietitians group have developed consensus dietetic statements that aim to harmonise dietary advice given to patients with PKU across the UK, but monitoring of statement adherence by health professionals and patients is required.

Objective: Mothers of premature infants confront barriers to coming to volume (CTV; ≥500 mL/day mother's own milk [MOM] by postpartum day 14), a strong predictor of continued MOM provision at neonatal intensive care unit (NICU) discharge. We sought to determine concentrations of secretory activation biomarkers (MOM sodium, total protein, lactose, and citrate) during the first 14 postpartum days and to describe relationships among these biomarkers, pumped MOM volume, CTV, and pumping frequency., Study Design: This descriptive observational study collected serial MOM samples, pumped MOM volume, and pumping frequency during the first 14 postpartum days in 16 breast pump-dependent mothers who delivered <33 weeks gestation. Daily biomarker concentrations were compared to published normal values for mothers of term infants. Relationships among biomarkers, pumped MOM volume, and pumping frequency were determined., Results: On postpartum day 5, only 40% of MOM samples revealed normal concentrations of all four biomarkers, and normalcy was not maintained throughout the first 14 days. All eight mothers (50%) who achieved CTV had normal concentrations for four biomarkers at 5.4 ± 3.5 days postpartum and had more cumulative pumping sessions by day 5 (p = 0.03). A dose-response relationship between number of normal biomarkers and pumped MOM volume was demonstrated for postpartum days 3 (p = 0.01) and 5 (p = 0.04)., Conclusion: Secretory activation is delayed in mothers who deliver prematurely and is closely tied to CTV, MOM volume, and pumping frequency. MOM biomarkers hold promise as objective research outcome measures and for point-of-care testing to identify and proactively manage mothers at risk for compromised lactation.

Objective: This study sought to determine the maternal prepregnancy, pregnancy, and delivery risk factors that predicted coming to volume (CTV; achieving pumped mother's own milk [MOM] volume ≥500 mLs/day) and the continuation of MOM provision through to discharge from the neonatal intensive care unit (NICU) in mothers and their very low birthweight (VLBW; <1,500 g at birth) infants., Study Design: Secondary analysis of prospectively collected data from 402 mothers of VLBW infants admitted to an urban NICU, including detailed MOM pumping records for a subset (51%) of the cohort. Analyses included inverse probability weighting, multivariate regression, and chi-square statistics., Results: In this high-risk cohort (51.2% black, 27.1% Hispanic, 21.6% white/Asian; 72.6% low income; 61.4% overweight/obese prepregnancy), CTV by day 14 was the strongest predictor of MOM feeding at NICU discharge (odds ratio [OR] 9.70 confidence interval [95% CI] 3.86-24.38, p < 0.01.). Only 39.5% of mothers achieved CTV by postpartum day 14, an outcome that was predicted by gestational age at delivery (OR 1.41, 95% CI 1.15-1.73, p < 0.01), being married (OR 3.66, 95% CI 1.08-12.39, p = 0.04), black race (OR 7.70, 95% CI 2.05-28.97, p < 0.01), cesarean delivery (OR 0.22, 95% CI 0.08-0.63, p = 0.01), and chorioamionitis (OR 0.14, 95% CI 0.02-0.82, p = 0.03)., Conclusion: Continued provision of MOM at NICU discharge can be predicted in the first 14 postpartum days on the basis of achievement of CTV. We posit that CTV can serve as a quality indicator for improving MOM feedings in the NICU and that lactation support resources should target this early critical postbirth period.

Introduction: 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency is an autosomal recessive disorder that usually presents in the neonatal period with vomiting, metabolic acidosis, hypoglycemia and absent ketonuria. Few cases are reported in the literature, and optimal dietary management and long term outcome are not fully understood., Case Report: We report a 2 year old girl with HMG-CoA-lyase deficiency who had limited fasting tolerance on a low protein diet, with several recurrent hospital admissions with severe hypoketotic hypoglycaemia and metabolic acidosis. We also review the dietary management and outcome of other reported cases in the literature., Discussion: In order to define optimal dietary treatment, it is important to collect higher numbers of case studies with detailed dietary management, fasting times and outcome.

Background: While black mothers initiate human milk (HM) provision at lower rates than non-black mothers in the United States, some neonatal intensive care units (NICUs) report similar initiation rates regardless of race/ethnicity for mothers of very-low-birth-weight (VLBW) infants. However, racial disparity frequently becomes evident in the proportion of black infants who continue to receive HM feedings at NICU discharge. Since social factors have been associated with differences in HM provision for term infants, we sought to identify differences in social factors associated with HM feeding at discharge based on race/ethnicity., Materials and Methods: A prospective cohort study of racially diverse mothers of VLBW infants measured social factors including maternal education, breastfeeding support, return to work/school, HM feeding goal, previous breastfeeding, or formula experience. Multivariate logistic regression modeling was applied to social factors to predict HM feeding at discharge. Additional regression models were created for racial/ethnic subgroups to identify differences., Results: For all 362 mothers, WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) eligibility and maternal goal near time of discharge of providing any HM negatively and positively predicted HM feeding at discharge, respectively. Perceived breastfeeding support from the infant's maternal grandmother negatively predicted HM feeding at discharge for black mothers., Conclusions: Future interventions to increase duration of HM provision in VLBW infants should focus on the establishment and maintenance of maternal HM feeding goals. Further studies of the familial support system of black mothers are warranted to determine multigenerational impact and potential interventions., Competing Interests: Statement No competing financial interests exist.

Background: Little is known about human milk (HM) feeding goals for mothers of very low birth weight (VLBW) (<1,500 g birth weight) infants, especially for black mothers, for whom rates of VLBW birth are higher and lactation rates lower. This study examined the establishment, modification, and achievement of HM feeding goals during neonatal intensive care unit (NICU) hospitalization for mothers of VLBW infants and the influence of maternal race and income., Materials and Methods: A prospective cohort study measured maternal HM feeding goals (exclusive [EHM], partial, none) predelivery and during three time intervals: day of life (DOL) 1-14, 15-28, and 29-72. Goal achievement compared the goal for the time interval with the proportion of HM feedings received by the infant. Goal establishment, modification, and achievement were examined using chi-squared and contingency tables., Results: Three hundred fifty-two mother-infant dyads (53% black; 70% low-income; mean birth weight, 1,048 g) were studied. Predelivery, 55% of mothers planned to provide EHM; fewer black and low-income mothers chose EHM. During DOL 1-14, 63% of mothers chose EHM, and predelivery racial differences disappeared. Only 10% of mothers chose exclusive at-breast EHM feedings. EHM feeding goals decreased during NICU hospitalization, especially for black mothers. Whereas most mothers met their HM feeding goals initially, achievement rates declined during hospitalization. Mothers' EHM goal achievement was not influenced by race or income., Conclusions: Mothers changed their predelivery HM feeding goals after birth of a VLBW infant. Longitudinally, HM feeding goals and achievement reflected less HM use, highlighting the need to target lactation maintenance in this population.

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study., Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling., Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders)., Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.

We report on a patient with Noonan syndrome due to SHOC2 missense mutation predicting p.Ser2Gly, recently described in association with Noonan syndrome. The male infant presented with fetal distress requiring premature delivery at 32 weeks and was noted to have dysmorphic features, edema, hepatosplenomegaly, leukocytosis, thrombocytopenia, and respiratory distress following birth. An echocardiogram revealed hypertrophic cardiomyopathy with left ventricular outflow tract obstruction. The infant's cardiac lesion rapidly progressed, and he was discharged home for palliative care. Clinical testing of genes causative of Noonan syndrome and related disorders detected the previously reported, pathogenic, de novo SHOC2 missense mutation predicting p.Ser2Gly. The patient's cardiac findings and features were not typical for those individuals previously reported with this SHOC2 mutation and thus expand the clinical phenotype., (Copyright © 2012 Wiley Periodicals, Inc.)

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts., (Copyright 2010 S. Karger AG, Basel.)

Background: We hypothesized that the use of HbA1c testing would help identify postrenal transplant diabetes (PTDM)., Methods: In all, 199 adult kidney transplant recipients at least 3 months posttransplant without previous history of diabetes or elevated fasting blood sugar were studied. Medical history, a fasting blood glucose, calcineurin inhibitor blood level, and HbA1c were obtained. Primary outcome was the incidence of subjects with HbA1c > or =6.1%. The covariates were use of cyclosporine or tacrolimus, time posttransplant, body mass index (BMI) at transplant and change since transplant, current steroid dose, history of graft rejection, current fasting glucose, age, and race. Proportions were compared between HbA1c <6 and > or =6.1% using Fisher's exact test. Means were compared using Student's t test. Logistic regression was used to identify risk factors associated with elevated HbA1c., Results: Twenty subjects (10.1%) had an elevated HbA1c. High normal fasting glucose (P=0.003) and African American race (P=0.08, marginally significant) were found to be associated with an elevated HbA1c. Subjects with normal and abnormal HbA1c levels were otherwise similar. There was no difference in HbA1c in tacrolimus versus cyclosporine treated subjects or in the percent of subjects with elevated HbA1c between these groups., Conclusions: HbA1c levels were found to be more a more sensitive test than fasting blood glucose levels in PTDM, with 10.1% of all patients and 19.4% of blacks found to have an elevated HbA1c. HbA1c testing should be considered as a screening test for PTDM, especially in African Americans.

Background: Behavior change counseling is one of the most difficult and constant challenges faced by health providers. It has a significant impact on clinical outcomes as well as patient and provider satisfaction. By encouraging patients to participate in a partnership with health care professionals, Brief Negotiation offers techniques to motivate behavior change successfully. We review the key components of Brief Negotiation and describe how one large group model health maintenance organization was able to identify key staff members, develop educational opportunities and implement Brief Negotiation system-wide into standard care practices., Objectives: To expose a maximum number of health care professionals to a recommended model of behavior change counseling; to increase the satisfaction and confidence of health care professionals in counseling for behavior change; and to increase the likelihood of improved patient health outcomes., Method: Two departments created one-day, two-day, six-hour and one-to-two-hour skill-based programs targeted to physicians, nurse practitioners, care managers, clinical health educators, behavioral medicine specialists, physical therapists, pharmacists and medical assistants. Practice protocols, strategic departmental alliances and intranet sites complemented the educational interventions., Results: Over 1000 health care professionals have been exposed to the Brief Negotiation model in over two years. A mailed survey to graduates of the one- and two-day programs indicated that 67% of physicians and 79% of other health professionals felt more confident about working with patients on behavior change after having attended the Brief Negotiation program., Conclusions: System-wide professional development requires multiple exposures to the Brief Negotiation model, considerable resources for curriculum development, training time and follow-up, and credible clinical trainers. Questions remain about the amount of training needed for long-term clinician behavior change and for improved health outcomes in patients.

If collaboration, not unrestrained competition, is part of the answer to containing health care costs, providers must choose their partners carefully. Competition won't disappear. It's here to stay. But many in our industry have come to the conclusion that increased collaboration is necessary to preserve community health care resources and prevent wasteful duplication of services and technology. Managed competition--a combination of government regulation and free markets--means simply that collaboration and competition will coexist in a new health care environment evolving toward integrated delivery systems of varying kinds.