Ellen Chetwynd

Breastmilk is a novel source of stem cells with multilineage differentiation potential

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self‐renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self‐renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC‐like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self‐renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient‐specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. STEM Cells2012;30:2164–2174

Prevalence and Risk Factors for Early, Undesired Weaning Attributed to Lactation Dysfunction

BACKGROUND Breastfeeding durations in the United States fall short of public health objectives. We sought to quantify the prevalence and identify risk factors for early, undesired weaning that mothers attribute to physiologic difficulties with breastfeeding. METHODS We analyzed data from the Infant Feeding Practices Study (IFPS) II, a longitudinal study of US women. We defined disrupted lactation as early, undesired weaning attributed to at least two of the following three problems: breast pain, low milk supply, and difficulty with infant latch. We used logistic regression to estimate the association maternal body mass index (BMI), postpartum depressive symptoms, and disrupted lactation. RESULTS Of 4,902 women enrolled in the IFPS II, we analyzed 2,335 women who reported prenatal intention and breastfeeding initiation. The prevalence of disrupted lactation was 12 per 100 women (95% confidence interval [CI] 11, 13) during the first year of life. Women in this group weaned earlier (median 1.2 months, interquartile range [IQR] 0.5-2.8) than women without disrupted lactation (median 7.0 months, IQR 2.8-2.0, p<0.01). In multivariable-adjusted (MV-adj.) models, we found increased odds of disrupted lactation among overweight (odds ratio [OR] 1.6, 95% CI 1.1-2.3) or obese (OR 1.7, 95% CI 1.2-2.6) women, compared with women with a normal pregravid BMI. Maternal depressive symptoms at 2 months, defined as Edinburgh Postnatal Depression Scale ≥13, were also associated with disrupted lactation (MV-adj. OR 1.7, 95% CI 1.1-2.7). CONCLUSION In a longitudinal sample of US women, disrupted lactation affected one in eight mothers who initiated breastfeeding. These findings underscore the need for both improved early breastfeeding support and targeted research to define the underlying pathophysiology and to determine management strategies that will enable more mothers to achieve their breastfeeding goals.

Gene expression in breastmilk cells is associated with maternal and infant characteristics.

Breastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles of these cells and their associations with characteristics of the breastfeeding mother and infant are poorly understood. This study investigated factors associated with the cellular dynamics of breastmilk and explored variations amongst women. Genes representing different breastmilk cell populations including mammary epithelial and myoepithelial cells, progenitors, and multi-lineage stem cells showed great variation in expression. Stem cell markers ESRRB and CK5, myoepithelial marker CK14, and lactocyte marker α-lactalbumin were amongst the genes most highly expressed across all samples tested. Genes exerting similar functions, such as either stem cell regulation or milk production, were found to be closely associated. Infant gestational age at delivery and changes in maternal bra cup size between pre-pregnancy and postpartum lactation were associated with expression of genes controlling stemness as well as milk synthesis. Additional correlations were found between genes and dyad characteristics, which may explain abnormalities related to low breastmilk supply or preterm birth. Our findings highlight the heterogeneity of breastmilk cell content and its changes associated with characteristics of the breastfeeding dyad that may reflect changing infant needs.

Fluconazole for postpartum candidal mastitis and infant thrush.

This case report illustrates the difficulties inherent in treating candidal mastitis in lactating women and concurrent thrush in the breastfeeding baby. This mothers candidiasis vacillated from topical to ductal, depending on which medications were being used over the course of several months. Her babys oral thrush was unique in that there were never any white plaques visible on his oral mucosa. Ultimately, both mother and child were treated simultaneously with oral fluconazole, with a relief of symptoms in both individuals.

Temporal Trends in the Inflammatory Cytokine Profile of Human Breastmilk

A longer lifetime duration of breastfeeding may decrease the risk of breast cancer by reducing breast inflammation and mitigating inflammatory cytokine expression during postlactational involution. However, little is known about how the inflammatory cytokine profile in human breastmilk changes over time. To study temporal trends in breastmilk cytokine expression, we measured 80 human cytokines in the whey fraction of breastmilk samples from 15 mothers at 1, 4, 8, and 12 weeks postpartum. We used mixed models to identify temporal changes in cytokine expression and investigated parity status (multiparous vs. primiparous) as a potential confounder. Nine cytokines (monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein-78, hepatocyte growth factor, insulin-like growth factor-binding protein-1, interleukin-16, interleukin-8, macrophage colony-stimulating factor, osteoprotegerin, and tissue inhibitor of metallopeptidase-2) had significantly decreased expression with increasing breastfeeding duration; all nine have known roles in breast involution, inflammation, and cancer and may serve as biomarkers of changing breast microenvironment. No cytokine significantly increased in level over the study period. Total protein concentration significantly decreased over time (p<0.0001), which may mediate the association between length of breastfeeding and inflammatory cytokine expression. Parity status did not confound temporal trends, but levels of several cytokines were significantly higher among multiparous versus primiparous women. Our results suggest that inflammatory cytokine expression during lactation is dynamic, and expressed milk may provide a noninvasive window into the extensive biological changes that occur in the postpartum breast.

Recognition of International Board Certified Lactation Consultants by health insurance providers in the United States: results of a national survey of lactation consultants.

Background: Insurance coverage for lactation management is proposed by the United States Affordable Care Act. International Board Certified Lactation Consultants (IBCLCs) are key providers of lactation services. In order to inform national discussion, this study examines the scope of insurance reimbursement of IBCLC services. Objectives: An email survey of US IBCLCs (N = 10 495) in March 2011 was used to explore frequencies of (1) submission—how often lactation consults were submitted to insurance providers for reimbursement and (2) recognition—the proportion of submitted charges recognized by insurance providers. Methods: Results (N = 2045) were analyzed to describe patterns of submission and recognition by IBCLC work setting, job classification, and reimbursement strategy. Results: Many survey respondents did not know their submission (41%) or recognition (57%) levels. Multiple strategies were used for reimbursement of IBCLC services with large variations in recognition between strategies. Overall, less than 15% reported high levels of submissions to insurance providers. Moreover, of submitted encounters, only 4% were consistently recognized by insurance providers. Inpatient hospital IBCLCs were least likely to have consults recognized (3%), and private community IBCLCs were most frequently recognized (32%). Compared with using IBCLC credentials for submitting an encounter, using another clinical license was the most successful strategy for achieving recognition of IBCLC consults (crude risk ratio, 1.44; 95% confidence interval, 1.04-2.01; P = .02). Conclusion: IBCLCs provide key care to a vulnerable population. However, we found that these services are not consistently reimbursed. IBCLCs poorly communicate their health care activities to insurance providers, but insurance providers also inconsistently recognize and reimburse IBCLC care.

The intricacies of induced lactation for same-sex mothers of an adopted child.

The definition of a modern family is changing. In this case study, we describe the breastfeeding experience of a child receiving human milk from all 3 of his mothers: his 2 adoptive mothers, who induced lactation to nurse him, and his birth mother, who shared in his early feeding during the open adoption process and continued to pump and send milk to him for several months. We review the lactation protocol used by his adoptive mothers and the unique difficulties inherent in this multi-mother family dynamic. Both adoptive mothers successfully induced moderate milk production using a combination of hormonal birth control, domperidone, herbal supplements, and a schedule of breast pumping. However, because of the increased complexity of the immediate postpartum period and concerns with defining parental roles in a same-sex marriage, maintenance of milk production was difficult.

Cumulative Lactation and Onset of Hypertension in African-American Women

Hypertension affects nearly 1 of 3 women and contributes to cardiovascular disease, the leading cause of death in the United States. Breastfeeding leads to metabolic changes that could reduce risks of hypertension. Hypertension disproportionately affects black women, but rates of breastfeeding among black women lag behind those in the general population. In the Black Womens Health Study (n = 59,001), we conducted a nested case-control analysis using unconditional logistic regression to estimate the association between breastfeeding and incident hypertension at ages 40-65 years using data collected from 1995 to 2011. Controls were frequency-matched 2:1 to 12,513 hypertensive women by age and questionnaire cycle. Overall, there was little evidence of association between ever breastfeeding and incident hypertension (odds ratio = 0.97, 95% confidence interval: 0.92, 1.02). However, age modified the relationship (P = 0.02): Breastfeeding was associated with reduced risk of hypertension at ages 40-49 years (odds ratio = 0.92, 95% confidence interval: 0.85, 0.99) but not at older ages. In addition, risk of hypertension at ages 40-49 years decreased with increasing duration of breastfeeding (P for trend = 0.08). Our results suggest that long-duration breastfeeding may reduce the risk of incident hypertension in middle age. Addressing breastfeeding as a potential preventative health behavior is particularly compelling because it is required for only a discrete period of time.

A Pilot Study on the Protein Composition of Induced Nonpuerperal Human Milk

Background: Our understanding of the components of human puerperal milk is extensive and increasing, yet the literature on nonpuerperal human milk has been limited to studies that measure the success of induced lactation. Objective: This study aimed to describe the composition of total protein and key bioactive proteins when lactation is induced in nonpuerperal women. Methods: Two women who induced lactation in the absence of pregnancy provided weekly milk samples over a 2-month period for analysis of total protein, secretory immunoglobulin A (sIgA), lysozyme, and lactoferrin. Composition was compared to the mature milk of 3 puerperal control subjects who were 11 months postpartum. Results: Median total protein for subject A was 2.30 g/dL (interquartile range [IQR] = 0.46) and showed a significant downward trend over time (P < .0001), whereas the median total protein for subject B was 2.21 g/dL (IQR = 0.18) and showed a nonsignificant decline (P = .232). Total protein in both nonpuerperal subjects was elevated compared to control subjects. Secretory IgA activity declined for both nonpuerperal subjects over time, whereas lysozyme concentrations increased over time. Both sIgA and lysozyme approached the levels seen in the puerperal controls. Lactoferrin levels remained stable for both nonpuerperal subjects and were elevated compared to puerperal milk samples. Conclusion: This pilot study suggests that nonpuerperal milk has similar or higher levels of total protein, sIgA, lactoferrin, and lysozyme compared to puerperal, mature milk at 11 months postpartum, which warrants more attention as adoptive mothers increasingly choose to induce lactation.

Selected abstracts from the Breastfeeding and Feminism International Conference 2016

Table of contentsA1. Infant feeding and poverty: a public health perspective in a global contextLisa H. AmirA2. Mothers’ experiences with galactagogues for lactation: an exploratory cross sectional studyAlessandra Bazzano, Shelley Thibeau, Katherine P. TheallA3. The motherhood journey and breastfeeding: from self-efficacy to resilience and social stigmaAnna Blair, Karin CadwellA4. Breastfeeding as an evolutionary adaptive behaviorEmily A. BronsonA5. Conflict-of-interest in public health policy: as real as that logo on your websiteElizabeth C. BrooksA6. Co-opting sisterhood and motherhood: behind the scenes of Similac’s aggressive social media campaignsJodine ChaseA7. The exclusion of women from the definition of exclusive breastfeedingEllen Chetwynd, Rebecca Costello, Kathryn WoukA8. Healthy maternity policies in the workplace: a state health department’s experience with the “Bring Your Infant to Work” programLindsey Dermid-GrayA9. Implications for a paradigm shift: factors related to breastfeeding among African American womenStephanie Devane-Johnson, Cheryl Woods Giscombe, Miriam LabbokA10. Social experiences of breastfeeding: building bridges between research and policy: an ESRC-funded seminar series in the UKSally DowlingA11. Manager’s perspectives of lactation breaksMelanie FraserA12. The challenging second night: a dialogue from two perspectivesJane Grassley, Deborah McCarter-Spaulding, Becky SpencerA13. The role of lactation consultants in two council breastfeeding services in Melbourne, Australia – some preliminary impressionsJennifer Hocking, Pranee LiamputtongA14. Integrating social marketing and community engagement concepts in community breastfeeding programsSheree H. Keitt, Harumi Reis-ReillyA15. What happens before and after the maternity stay? Creating a community-wide Ten Steps approachMiriam LabbokA16. #RVABREASTFEEDS: cultivating a breastfeeding-friendly communityLeslie LytleA17. Public health vs. free trade: a longitudinal analysis of a global policy to protect breastfeedingMary Ann MerzA18. Legislative advocacy and grassroots organizing for improved breastfeeding laws in VirginiaKate NoonA19. Breastfeeding and the rights of incarcerated womenKrista M OlsonA20. Barriers and support for Puerto Rican breastfeeding working mothersAna M. Parrilla-Rodríguez, José J. Gorrín-Peralta Melissa Pellicier, Zeleida M. Vázquez-RiveraA21. Pumping at work: a daily struggle for Puerto Rican breastfeeding mothers in spite of the lawMelissa PellicierA22. “I saw a wrong and I wanted to stand up for what I thought was right:” a narrative study on becoming a breastfeeding activistJennifer L. PembertonA23. Peer breastfeeding support: advocacy and actionCatherine McEvilly PestlA24. Good intentions: a study of breastfeeding intention and postpartum realities among first-time Central Brooklyn mothersJennifer Pierre, Philip Noyes, Khushbu Srivastava, Sharon Marshall-TaylorA25. Women describing the infant feeding choice: the impact of the WIC breastfeeding classes on infant feeding practices in Ionia, MichiganJennifer Proto, Sarah Hyland Laurie BrinksA26. Local and state programs and national partnership to reduce disparities through community breastfeeding supportHarumi Reis-Reilly, Martelle Esposito, Megan PhillippiA27. Beyond black breastfeeding week: instagram image content analysis for #blackwomendobreastfeed/#bwdbfCynthia L. Sears, Delores James, Cedric Harville, Kristina CarswellA28. Stakeholder views of breastfeeding education in the K-12 environment: a review of the literatureNicola Singletary, L. Suzanne Goodell, April FoglemanA29. “The Breastfeeding Transition”: a framework for explaining changes in global breastfeeding rates as related to large-scale forces shaping the status of womenPaige Hall SmithA30. Breastfeeding, contraception, and ethics, oh my! Advocacy and informed decision-making in the post-partum periodAlison M. Stuebe, Amy G. Bryant, Anne Drapkin LyerlyA31. A hard day’s night: juggling nighttime breastfeeding, sleep, and workCecilia TomoriA32. Empowering change in Indian country through breastfeeding educationAmanda L. Watkins, Joan E. DodgsonA33. Servants and “Little Mothers” take charge: work, class, and breastfeeding rates in the early 20th-century U.S.Jacqueline H. Wolf