Lactation Insufficiency Research Articles

Chronic Lactation Insufficiency Is a Public Health Issue: Commentary on "We Need Patient-Centered Research in Breastfeeding Medicine" by Stuebe. Breastfeed Med 2021;16:349-350.

Chronic Lactation Insufficiency Is a Public Health Issue: Commentary on "We Need Patient-Centered Research in Breastfeeding Medicine" by Stuebe. Breastfeed Med 2021;16:349-350.

Study and Experimental Validation of the Functional Components and Mechanisms of Hemerocallis citrina Baroni in the Treatment of Lactation Deficiency.

The function of Hemerocallis citrina Baroni (daylily) on promoting lactation is reported in several ancient Chinese medicine books. However, nowadays, there is no conclusive data to support this statement. In this study, we investigated the effect of Hemerocallis citrina Baroni extract (HCE) on lactation insufficiency in chronic unpredictable mild stress (CUMS) dams and further explored the mechanism and functional components through network pharmacology. The results showed that HCE could increase the offspring’s weight, serum prolactin (PRL), and oxytocin (OT) level of CUMS dams. Network pharmacology analysis revealed that the facilitation of HCE on lactation is the result of the comprehensive action of 62 components on 209 targets and 260 pathways, among this network, quercetin, kaempferol, thymidine, etc., were the vital material basis, signal transducer and activator of transcription 3 (STAT3), mitogen activity protein kinase 1 (MAPK1), tumor protein P53 (TP53), etc., were the core targets, and the prolactin signaling pathway was the core pathway. In addition, verification test results showed that HCE regulated the abnormal expression of the prolactin signaling pathway, including STAT3, cyclin D1 (CCND1), MAPK1, MAPK8, nuclear factor NF-kappa-B p105 subunit (NFKB1), and tyrosine-protein kinase (JAK2). In conclusion, HCE exhibited a facilitation of lactation insufficiency, in which quercetin, kaempferol, thymidine, etc., were the most important material basis. The mechanism of this promotional effect is mediated by the prolactin signaling pathway in mammary gland.

We Need Patient-Centered Research in Breastfeeding Medicine

Breastfeeding MedicineVol. 16, No. 4 President's CornerWe Need Patient-Centered Research in Breastfeeding MedicineAlison StuebeAlison Stuebe—Alison Stuebe, MD, MSc, President, Academy of Breastfeeding MedicineSearch for more papers by this authorPublished Online:12 Apr 2021https://doi.org/10.1089/bfm.2021.29181.amsAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"We Need Patient-Centered Research in Breastfeeding Medicine." Breastfeeding Medicine, 16(4), pp. 349–350FiguresReferencesRelatedDetailsCited byMeasures of Maternal Metabolic Health as Predictors of Severely Low Milk Production Laurie A. Nommsen-Rivers, Erin A. Wagner, Dayna M. Roznowski, Sarah W. Riddle, Laura P. Ward, and Amy Thompson12 July 2022 | Breastfeeding Medicine, Vol. 17, No. 7Chronic Lactation Insufficiency Is a Public Health Issue: Commentary on “We Need Patient-Centered Research in Breastfeeding Medicine” by Stuebe. Breastfeed Med 2021;16:349–350. Helen Shere, Laurel Weijer, Harriet Dashnow, L. Elizabeth Moreno, Susanna Foxworthy Scott, and Helen Baker7 December 2021 | Breastfeeding Medicine, Vol. 16, No. 12 Volume 16Issue 4Apr 2021 InformationCopyright 2021, Mary Ann Liebert, Inc., publishersTo cite this article:Alison Stuebe.We Need Patient-Centered Research in Breastfeeding Medicine.Breastfeeding Medicine.Apr 2021.349-350.http://doi.org/10.1089/bfm.2021.29181.amsPublished in Volume: 16 Issue 4: April 12, 2021PDF download

Exploring the Prescribing Process of Domperidone for Low Milk Supply: A Qualitative Study Among Mothers, IBCLCs, and Family Doctors.

BackgroundWhen mothers are confronted with milk supply problems, taking domperidone is regularly suggested. However, domperidone has been associated with sudden cardiac death and caution in prescribing is advised. In 2016, a multidisciplinary group of authors from a tertiary academic hospital (Erasmus MC) published a clinical protocol in a leading Dutch physicians’ journal to support Dutch family physicians in prescribing domperidone to stimulate lactation.Research aimTo explore consumer and health care provider perspectives and experiences regarding the prescribing of domperidone for lactation insufficiency following publication of a national clinical protocol.MethodsA cross-sectional qualitative study was performed using semi-structured interviews (N = 40) based on a topic list covering the prescribing process. Participants were mothers (n = 18) who had been advised to try domperidone to boost their milk supply between November 2016 and May 2018, their International Board Certified Lactation Consultants (n = 9), and their family physicians (n = 15). Another group of participants (mothers; n = 6) answered short questionnaires. All interviews were recorded, transcribed and analyzed using ATLAS.ti software. The resulting list of codes was organized according to the topics.ResultsIn the process leading to domperidone use to stimulate lactation, participant family physicians relied on the IBCLC, pharmacist, or mother to guide the prescription of domperidone, often citing the published national clinical protocol as back up. The medical safeguards incorporated in the protocol (e.g., taking medical history, physical exam, performing electrocardiograms, limiting dosage) were usually not implemented.ConclusionsThough the availability of a national clinical protocol in which the prescribing of domperidone for lactation is supported appeared to increase the willingness of participant family physicians to prescribe, gaps were identified between clinical practice and this clinical protocol for prescribing domperidone.

Mucosal Immunity and Liver Metabolism in the Complex Condition of Lactation Insufficiency.

Lactation insufficiency is variously defined and includes the inability to produce milk, not producing enough milk to exclusively meet infant growth requirements, and pathological interruption of lactation (e.g., mastitis). Of women with intent-to-breastfeed, lactation insufficiency has been estimated to affect 38%-44% of newly postpartum women, likely contributing to the nearly 60% of infants that are not breastfed according to the World Health Organization's guidelines. To date, research and clinical practice aimed at improving feeding outcomes have focused on hospital lactation support and education, with laudable results. However, researchers' reports of recent rodent studies concerning fundamental lactation biology have suggested that the underlying pathologies of lactation insufficiency may be more nuanced than is currently appreciated. In this article, we identify mucosal biology of the breast and lactation-specific liver biology as two under-researched aspects of lactation physiology. Specifically, we argue that further scientific inquiry into reproductive state-dependent regulation of immunity in the human breast will reveal insights into novel immune based requirements for healthy lactation. Additionally, our synthesis of the literature supports the hypothesis that the liver is an essential player in lactation-highlighting the potential that pathologies of the liver may also be associated with lactation insufficiency. More research into these biologic underpinnings of lactation is anticipated to provide new avenues to understand and treat lactation insufficiency.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

Oral galactagogues (natural therapies or drugs) for increasing breast milk production in mothers of non-hospitalised term infants.

An endocrine hypothesis to explain obesity-related lactation insufficiency in breastfeeding mothers.

In this Research Reflection I shall develop and validate the hypothesis that lactation insufficiency in obese breastfeeding mothers has an endocrine explanation. I shall not present data, but I shall review pertinent literature to show that obesity is associated with a partial or sometimes complete failure to initiate and maintain lactation, and critically examine the belief that this is due to psychosocial factors, a failure of prolactin secretion or both. Since progesterone is inhibitory to lactogenesis and oestrogens are inhibitory to milk secretion, I shall then explore the possibility that these steroids are linked to lactation failure, through sequestration of progesterone and aromatization of oestrogen in mammary adipose tissue. I shall conclude by describing experimental approaches in animal models that could be used to test this hypothesis.

TDP-43 facilitates milk lipid secretion by post-transcriptional regulation of Btn1a1 and Xdh

Milk lipid secretion is a critical process for the delivery of nutrition and energy from parent to offspring. However, the underlying molecular mechanism is less clear. Here we report that TDP-43, a RNA-binding protein, underwent positive selection in the mammalian lineage. Furthermore, TDP-43 gene (Tardbp) loss induces accumulation of large lipid droplets and severe lipid secretion deficiency in mammary epithelial cells to outside alveolar lumens, eventually resulting in lactation failure and pup starvation within three weeks postpartum. In human milk samples from lactating women, the expression levels of TDP-43 is positively correlated with higher milk output. Mechanistically, TDP-43 exerts post-transcriptional regulation of Btn1a1 and Xdh mRNA stability, which are required for the secretion of lipid droplets from epithelial cells to the lumen. Taken together, our results highlights the critical role of TDP-43 in milk lipid secretion, providing a potential strategy for the screening and intervention of clinical lactation insufficiency.

A Prospective, Randomized, Placebo-controlled Comparative Study of Amino Acid Supplementation in Lactation Insufficiency

ABSTRACT Objective Our study evaluates the clinical efficacy of intravenous (i/v) amino acids in the prevention of lactation insufficiency and improvement of neonatal weight gain. Design A prospective, randomized, open-label, placebo-controlled clinical trial is reported. Population or sample This study recruited 305 lactating mothers of age-group, 22–35 years. Methods Test group, n = 152, received i/v amino acid infusion, 500 mL, as study drug once daily for 4 days, and control group, n = 153, received normal saline as placebo, 500 mL od for 4 days. Main outcome measures We studied the efficacy and safety of i/v amino acids in the prevention of lactation insufficiency. We further evaluated the role of maternal amino acid supplementation in ameliorating physiological weight loss and overall neonatal weight gain. Results Lactation onset was reported in 86.3% of mothers in the amino acid group at day 0 as compared to 32.23% in the control group (p value < 0.001). Lactation was achieved by all the mothers in the study group by day 1 itself with two doses of i/v amino acids (p value < 0.001). An increase in neonatal weight was observed in the amino acid group, (2.900 ± 0.488, p value = 0.001) compared with the control group at 2 weeks (2.716 ± 0.484, p value = 0.001). Conclusion Maternal amino acid supplementation is proven to be both efficacious and safe in augmenting breast milk production, thereby preventing lactation insufficiency. It effectively prevented neonatal physiological weight loss at 2 weeks and promoted substantial weight gain over a period of a month after birth. How to cite this article Nagarathnamma R, Pooja Bhushan, Dutta T, Ezhil Arasan R. A Prospective, Randomized, Placebo-controlled Comparative Study of Amino Acid Supplementation in Lactation Insufficiency. J South Asian Feder Obst Gynae 2020;12(6):408–414.

“It was all taken away”: Lactation, embodiment, and resistance among mothers caring for their very-low-birth-weight infants in the neonatal intensive care unit

The prevalence of infants born before 37 weeks of gestation continues to rise in the United States. Advances in neonatology have led to improved survival rates among preterm infants, including those born at a very-low-birth-weight (VLBW). Exclusive human milk feeding is a therapeutic intervention for VLBW preterm infants, and mothers are encouraged to provide their own milk. Yet, it is well-established that mothers and infants may face extraordinarily complicated lactation and infant feeding challenges in NICU settings, many of which emanate from birth trauma. The purpose of this study is to gain a deeper understanding of the ways in which the hyper-medicalized management of preterm birth and infant feeding in NICU environments affect mothers' postpartum health and well-being. Seventeen mothers of VLBW preterm infants were interviewed August 2016–June 2017 within three years of their infant's NICU discharge about their feeding decisions and experiences. Narrative analysis yielded five themes: (1) the physical and emotional trauma of giving birth prematurely impacted mothers' lactation experiences; (2) separation from their infants intensified mothers' suffering and disrupted lactation; (3) mothers experienced being marginalized in their infant's NICU care; (4) mothers practiced embodied forms of resistance to cope with both trauma and marginalization; and (5) skilled support was central to mothers' positive lactation experiences in the NICU. We draw upon feminist theory in the anthropology of reproduction to examine the fundamental hierarchies of power in U.S. neonatal critical care systems that fracture mothers' interembodied relationships to their newborns, exacerbate lactation failure, and engender traumatic postpartum neglect. Moreover, we theorize mothers' expressions of suffering in the context of preterm birth and lactation insufficiency as idioms of distress engendered by the violence of neglectful care. Narrative inquiry is instrumental to designing structural transformations in the systems of care available to mothers of preterm infants who are admitted to a NICU.

What Evidence Do We Have for Pharmaceutical Galactagogues in the Treatment of Lactation Insufficiency?-A Narrative Review.

Inadequate breast milk supply is a frequently reported reason for early discontinuation of breastfeeding and represents a critical opportunity for intervening to improve breastfeeding outcomes. For women who continue to experience insufficient milk supply despite the utilisation of non-pharmacological lactation support strategies, pharmacological intervention with medications used to augment lactation, commonly referred to as galactagogues, is common. Galactagogues exert their pharmacological effects through altering the complex hormonal milieu regulating lactation, particularly prolactin and oxytocin. This narrative review provides an appraisal of the existing evidence regarding the efficacy and safety of pharmaceutical treatments for lactation insufficiency to guide their use in clinical practice. The greatest body of evidence surrounds the use of domperidone, with studies demonstrating moderate short-term improvements in breast milk supply. Evidence regarding the efficacy and safety of metoclopramide is less robust, but given that it shares the same mechanism of action as domperidone it may represent a potential treatment alternative where domperidone is unsuitable. Data on remaining interventions such as oxytocin, prolactin and metformin is too limited to support their use in clinical practice. The review provides an overview of key evidence gaps and areas of future research, including the impacts of pharmaceutical galactagogues on breast milk composition and understanding factors contributing to individual treatment response to pharmaceutical galactagogues.

Use of shared milk among breastfeeding mothers with lactation insufficiency.

Social media platforms have facilitated the use of shared breast milk for infant feeding since 2010. This study aims to assess the prevalence of shared milk use among breastfeeding mothers with insufficient milk supply; and compare shared milk users with non-users. Data were collected from breastfeeding mothers with low milk supply through an anonymous Internet-based survey in 2013. Shared milk users were those who used shared milk for at least 10% of their infant's needs; the rest were considered non-users. Chi-square comparisons between these groups assessed reasons and information sources for supplementation options; breastfeeding and supplement choice satisfaction; and breastfeeding duration. One hundred thirty-eight (29.1%) of 475 participants reported shared milk use. Healthfulness and reduced risk were most important to users (p<.001), whereas non-users cited convenience and lack of knowledge about other options (p<.001). Users reported receiving information from medical/breastfeeding professionals and online discussion forums, whereas non-users were more likely to not seek information about supplementation options. Users of shared milk were significantly more likely to provide breast milk at 6months (59.3% vs. 39.6%, p=.001) and be satisfied with their supplementation choice (p<.001) compared with non-users. For women with self-reported lactation insufficiency, this study found that shared milk users were more likely to breastfeed longer, seek resources, identify healthful options, and report greater satisfaction with their supplementation choice than non-users. Importantly, shared milk may play a role in achieving U.S. Healthy People 2020 targets for breastfeeding duration.

Dysregulation of ZnT2‐Mediated Zn Homeostasis Impairs Epithelial Polarity And Breast Differentiation

Epithelial polarity is essential for the architecture and function of the mammary gland. We previously found that the loss of the vesicular zinc (Zn) transporter ZnT2 in ZnT2‐null mice compromises polarity, reduces STAT5 activation and impairs mammary gland differentiation. Here, we aimed to determine how the loss of ZnT2 impairs polarity and mammary gland differentiation. We used ZnT2‐attenuated mammary epithelial cells (MECs) in vitro and hypothesized that the loss of ZnT2‐mediated Zn transport dysregulates (PTEN), an epithelial polarity factor that disrupts spatial orientation of polarity, which subsequently impairs prolactin‐mediated Jak2/STAT5 signaling. First, we found that without the ability to sequester Zn into vesicles via ZnT2, Zn accumulated in the cytoplasm and significantly reduced PTEN expression. Moreover, ZnT2‐attenuated MECs had reduced membrane expression of, Annexin A2, a protein involved in apical membrane transport, and disrupted localization of ZO‐1, a protein critical for tight junction assembly, indicating impaired spatial orientation. Consequently, ZnT2‐attenuated MECs failed to differentiate into 3D mammospheres with expanded alveolar lumen. Importantly, we showed that the loss polarity disrupted cell surface localization of the principal lactogenic hormone receptor, prolactin receptor, and reduced downstream Jak2/STAT5 signaling, collectively indicating that cytoplasmic Zn accumulation dysregulates epithelial polarity and mammary differentiation. Our recent studies in breastfeeding women identified several non‐synonymous genetic variants in ZnT2 that result in “loss‐of‐function”. To investigate effects of these variants (ZnT2K66N and ZnT2Q71H) on MEC polarity, we transfected MECs to express these ZnT2 variants and found that expression increased cytoplasmic Zn and reduced PTEN expression in MECs, implicating defects of ZnT2 function in breast differentiation in women. Taken together, these results establish that ZnT2‐mediated Zn homeostasis is critical for maintaining epithelial polarity and regulating prolactin signaling for proper mammary gland differentiation and this suggests that “loss‐of‐function” variants of ZnT2 may be associated with impaired breast differentiation and lactation insufficiency in women.Support or Funding InformationIntramural funds to SLK

Association Between Maternal Pre‐Pregnant Body Mass Index and Breast Markers for Lactation Insufficiency Among Mothers With Self‐Reported Low Milk Supply

BackgroundWomen with high pre‐pregnant body mass index (BMI) have lower rates of breastfeeding exclusivity and duration than their normal‐BMI counterparts. Animal models suggest that the physiology of obesity may corrupt normal mammary gland development and function. This study sought to identify an association in humans between pre‐pregnant BMI and physical characteristics that may be predictive of disrupted lactation due to insufficient glandular development of the breast.MethodsThe data for this analysis was drawn from a 2013 study of mothers who intended to exclusively breastfeed but believed they did not produce sufficient milk to do so. The mixed‐methods, 141‐item questionnaire was available online and participants were recruited through Internet platforms for mothers with breastfeeding problems and email listservs for breastfeeding supporters. Pre‐pregnant BMI was calculated from self‐reported pre‐pregnant height and weight. Those with BMI &gt;= 25 were classified as high BMI. Respondents who reported little or no breast changes in pregnancy, little or no breast changes postpartum, wide ( &gt; 1.5 inches or 3.8 cm) intramammary space, and tubular breast shape were classified as having markers of insufficient glandular development. Logistic regression was used to test for an association between pre‐pregnant BMI and breast markers that may be predictive of lactation insufficiency.Results57.5% of respondents (N = 1022) reported a pre‐pregnant BMI of 25 or greater. High pre‐pregnant BMI was strongly and significantly associated (OR = 2.42, 95% CI: 1.79, 3.26; p &lt; .0001) with having the four markers suggestive of insufficient breast gland development.ConclusionWomen with high pre‐pregnant BMI may be more likely to also have insufficiently developed breasts, resulting in reduced capacity for exclusive breastfeeding.Support or Funding InformationNone. This study was undertaken in partial fulfillment of the first author's Master of Public Health thesis project.

Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation

The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating mammary gland and non-secreting MECs, highlighting the importance of ZnT2 in general mammary gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on mammary gland development, function during lactation, and milk composition. We found that ZnT2 was primarily expressed in MECs and to a limited extent in macrophages in the nulliparous mammary gland and loss of ZnT2 impaired mammary expansion during development. Secondly, we found that lactating ZnT2-null mice had substantial defects in mammary gland architecture and MEC function during secretion, including fewer, condensed and disorganized alveoli, impaired Stat5 activation, and unpolarized MECs. Loss of ZnT2 led to reduced milk volume and milk containing less protein, fat, and lactose compared with wild-type littermates, implicating ZnT2 in the regulation of mammary differentiation and optimal milk production during lactation. Together, these results demonstrate that ZnT2-mediated zinc transport is critical for mammary gland function, suggesting that defects in ZnT2 not only reduce milk zinc concentration but may compromise breast health and increase the risk for lactation insufficiency in lactating women.

Inflammatory Mediators in Mastitis and Lactation Insufficiency

Mastitis is a common inflammatory disease during lactation that causes reduced milk supply. A growing body of evidence challenges the central role of pathogenic bacteria in mastitis, with disease severity associated with markers of inflammation rather than infection. Inflammation in the mammary gland may be triggered by microbe-associated molecular patterns (MAMPs) as well as danger-associated molecular patterns (DAMPs) binding to pattern recognition receptors such as the toll-like receptors (TLRs) on the surface of mammary epithelial cells and local immune cell populations. Activation of the TLR4 signalling pathway and downstream nuclear factor kappa B (NFkB) is critical to mediating local mammary gland inflammation and systemic immune responses in mouse models of mastitis. However, activation of NFkB also induces epithelial cell apoptosis and reduced milk protein synthesis, suggesting that inflammatory mediators activated during mastitis promote partial involution. Perturbed milk flow, maternal stress and genetic predisposition are significant risk factors for mastitis, and could lead to a heightened TLR4-mediated inflammatory response, resulting in increased susceptibility and severity of mastitis disease in the context of low MAMP abundance. Therefore, heightened host inflammatory signalling may act in concert with pathogenic or commensal bacterial species to cause both the inflammation associated with mastitis and lactation insufficiency. Here, we present an alternate paradigm to the widely held notion that breast inflammation is driven principally by infectious bacterial pathogens, and suggest there may be other therapeutic strategies, apart from the currently utilised antimicrobial agents, that could be employed to prevent and treat mastitis in women.

Toll-Like Receptor 4 Regulates Lipopolysaccharide-Induced Inflammation and Lactation Insufficiency in a Mouse Model of Mastitis1

Lactation mastitis is a debilitating inflammatory breast disease in postpartum women. Disease severity is associated with markers of inflammation rather than bacterial load, suggesting that immune-signaling pathways activated in the host are important in the disease pathology. The role of the innate pattern recognition receptor toll-like receptor 4 (TLR4) in progression and resolution of mastitislike disease was investigated in a mouse model. Lipopolysaccharide in Matrigel (10 μg/10 μl) was administered into the teat canal of lactating Tlr4 null mutant and wild-type mice to induce a localized area of inflammation. Mastitis induction resulted in a marked influx of RB6-positive neutrophils and F4/80-positive macrophages, which was higher in Tlr4(-/-) mice compared to wild-type mice. Tlr4 null mutation resulted in an altered immune-signaling fingerprint following induction of mastitis, with attenuated serum cytokines, including CXCL1, CCL2, interleukin 1 beta, and tumor necrosis factor alpha compared to wild-type mice. In both genotypes, the localized area of inflammation had resolved after 7 days, and milk protein was evident. However, the mammary glands of wild-type mice exhibited reduced capacity for milk production, with decreased percent area populated with glandular epithelium and decreased abundance of nuclear phosphorylated signal transducer and activator of transcription 5 compared to Tlr4 null mice. This study demonstrates that inflammatory pathways activated in the host are critically important in mastitis disease progression and suggests that lactation insufficiency associated with mastitis may be a consequence of TLR4-mediated inflammation, rather than the bacterial infection itself.

Allaitement après chirurgie mammaire : information des patientes

ObjectivesPartial mastectomy, augmentation and reduction mammaplasty are often operated on women who are not yet bothered by breastfeeding. The objectives of this study were to evaluate the information given to patients before surgery, and describe difficulties that mothers confront when starting breastfeeding in order to create a reference document about breastfeeding to inform patients who will undergo such surgery in the future. Material and methodsWe led one first study to evaluate the surgeons’ practice in the Reunion Island and a second retrospective and descriptive study upon patients. ResultsWe encountered the fact that few patients in childbearing age ask for information about breastfeeding before undergoing surgery, but surgeons do not systematically give such information either, even less before partial mastectomy. The impact of surgery on breastfeeding depends on the type of intervention and the surgical technique. Even though breastfeeding is possible, the mean period of breastfeeding after surgery is shorter and the most frequent difficulty encountered is lactation insufficiency, even more after reduction mammaplasty, periareolar incision, and nipple hypoesthesia after surgery. Discussion and conclusionThe information document that we tried to establish concerning breastfeeding after partial mastectomy, augmentation and reduction mammaplasty, may compensate patients’ lack of information and sums up all the complications described in our study and in the literature.

Clinical Update and Treatment of Lactation Insufficiency

Lactation is beneficial to mother’s health as well as provides specific nourishments, growth, and development to the baby. Hence, it is a nature’s precious gift for the infant; however, lactation insufficiency is one of the explanations mentioned most often by women throughout the world for the early discontinuation of breastfeeding and/or for the introduction of supplementary bottles. Globally, lactation insufficiency is a public health concern, as the use of breast milk substitutes increases the risk of morbidity and mortality among infants in developing countries, and these supplements are the most common cause of malnutrition. The incidence has been estimated to range from 23% to 63% during the first 4 months after delivery. The present article provides a literary search in English language of incidence, etiopathogensis, pathophysiology, clinical features, diagnosis, and current update on treatment of lactation insufficiency from different sources such as reference books, Medline, Pubmed, other Web sites, etc. Non-breast-fed infant are 14 times more likely to die due to diarrhea, 3 times more likely to die of respiratory infection, and twice as likely to die of other infections than an exclusively breast-fed child. Therefore, lactation insufficiency should be tackled in appropriate manner.

Experimental Autoimmune Breast Failure: A Model for Lactation Insufficiency, Postnatal Nutritional Deprivation, and Prophylactic Breast Cancer Vaccination

Mastitis is a substantial clinical problem in lactating women that may result in severe pain and abrupt termination of breastfeeding, thereby predisposing infants to long-term health risks. Many cases of mastitis involve no known infectious agent and may fundamentally be due to autoimmune-mediated inflammation of the breast. Herein, we develop a murine model of autoimmune mastitis and provide a detailed characterization of its resulting phenotype of breast failure and lactation insufficiency. To generate breast-specific autoimmunity, we immunized SWXJ mice with recombinant mouse α-lactalbumin, a lactation-dependent, breast-specific differentiation protein critical for production of lactose. Mice immunized with α-lactalbumin showed extensive T-cell-mediated inflammation in lactating normal breast parenchyma but none in nonlactating normal breast parenchyma. This targeted autoimmune attack resulted in breast failure characterized by lactation insufficiency and decreased ability to nurture offspring. Although immunization with α-lactalbumin had no effect on fertility and birth numbers, pups nursed by α-lactalbumin-immunized mice showed significantly disrupted growth often accompanied by kwashiorkor-like nutritional abnormalities, including alopecia, liver toxicity, and runting. This experimental model of autoimmune breast failure has useful applications for prophylactic breast cancer vaccination and for addressing inflammatory complications during breastfeeding. In addition, this model is suited for investigating nutritionally based "failure-to-thrive" issues, particularly regarding the long-term implications of postnatal nutritional deprivation.