Short-term Breastfeeding Research Articles

Beneficial effects of short-term breastfeeding versus non-breastfeeding in early life against childhood obesity: findings from the US-based population study NHANES

BackgroundBreastfeeding is widely recognized for its potential to reduce childhood obesity. However, research investigating these benefits in children breastfed for a short duration (up to 6 months) remains limited despite this being a common practice globally.MethodsThis study focused on a population breastfed for 6 months or less to determine the potential benefits of short-term breastfeeding for preventing childhood obesity. Data were collected from five survey cycles of an US-based population study (the National Health and Nutrition Examination Survey (NHANES)), spanning 2009–2020. A sample of 3,211 children aged 2–6 years was selected, including 1,373 never breastfed and 1,838 ever breastfed. Logistic regression analysis examined the direct association between short-term breastfeeding and childhood obesity. Subsequent subgroup analyses were conducted. Additionally, stratified logistic regression explored the relationship between childhood obesity and the introduction of other early nutrition in both ever-breastfed and never-breastfed children.ResultsOverall, breastfeeding for 6 months or less did not directly prevent childhood obesity. However, among participants with older mothers (aged 35 or above), short-term breastfeeding was associated with a lower risk of childhood obesity compared to never being breastfed (OR 0.31, 95% CI: 0.17, 0.59). Similarly, children aged 3–4 years who were breastfed for > 3 ~ 6 months exhibited a lower obesity risk (OR 0.56, 95% CI: 0.35, 0.89). In ever-breastfed children, delayed infant formula introduction was linked to a lower risk of obesity (P-trend < 0.05: introduction at age ≤ 1 vs. >1 ~ 3 vs. >3 months). Conversely, for non-breastfed children, introducing milk (other than breast milk or formula) later (≥ 12 versus < 12 months) and introducing alternatives to whole cow’s milk were associated with lower obesity risks (OR 0.54, 95% CI: 0.37, 0.78; OR 0.21, 95% CI: 0.08, 0.60, respectively). Notably, these trends were not observed in ever-breastfed children.ConclusionsShort-term breastfeeding may offer some benefits in preventing childhood obesity for specific populations. Additionally, it could potentially mitigate risks associated with the introduction of formula and cow’s milk at inappropriate times.

Abstract PO2-28-04: Pregnancy-associated relapse of triple-negative breast cancer

Abstract Introduction: Pregnancy Triple-negative breast cancer(TNMC) is the absence of ER PR and HER2 receptor expression. It constitutes about 15-20% of all breast cancers and is known to be the aggressive form with a high relapse rate (1). Interestingly, it usually affects women aged &amp;lt; 40 and has a low survival rate in African-American females. This case is a typical presentation of a 38-year-old young woman with PMH of T2NO right triple-negative breast cancer diagnosed in 2017 s/p right mastectomy with sentinel LN biopsy, received immunotherapy and chemotherapy, has been cancer-free for two years, and developed metastatic cancer during her pregnancy. In this case, we understand the diagnostic and therapeutic challenges of TNBC during pregnancy. Case: A 38-year-old African American woman, G0, T2NO triple negative invasive ductal carcinoma, underwent a right breast mastectomy and sentinel LN biopsy. She received treatment with (Anti-PD-L1 Antibody) concomitant with weekly paclitaxel and Doxorubicin/Cyclophosphamide (AC) chemotherapy. However, she had a residual 4cm tumor for which she was treated with adjuvant therapy with capecitabine for six months. A repeat Mammogram in 2019 showed no evidence of malignancy. In 2021, the patient was G2P2L1, admitted to the hospital after having a seizure. CT reported cystic/necrotic left parietal lesion mass effect with 8mm right-sided midline shift with metastasis to lungs and abdominal wall. She underwent L parietal craniectomy with resection of the tumor. At 32 weeks of gestation , chemotherapy with carboplatin and paclitaxel was given after her C-section and Gamma knife radiosurgery for metastatic lesions. She developed super refractory seizures, was induced into a coma with therapeutically anesthetic agents, and passed eventually. Discussion: Little literature exists on pregnancy-associated relapse of triple-negative breast cancer and its deterioration. Our patient was in remission for two years and was diagnosed with metastatic cancer during her second pregnancy. John et al., (2018) discussed an interesting association between breastfeeding, parity, and occurrence of TNBC, that there is a two-fold increased risk of developing TNBC with high parity(3 full-term pregnancies) and short-term breastfeeding (&amp;lt; 12 months) (2). Studies have also shown that cancers during or postpartum pregnancy are aggressive with more tumor burden and metastasize to the lungs, liver, and brain, which is consistent with our patient. (3) Conclusion: Pregnancy-associated breast cancer is diagnostically and therapeutically challenging during or in the postpartum period and with a high propensity of the triple-negative type. It requires a multidisciplinary team approach, awareness in the African American population, clinical suspicion of breast mass during pregnancy warrants imaging, and prolonged breastfeeding postpartum. Diagnosis is usually delayed due to pregnancy, and more research is needed on the diagnostic modalities during pregnancy for early treatment initiation. References Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417. PMID: 35145999; PMCID: PMC8824427. John EM, Hines LM, Phipps AI, et al. Reproductive history, breast-feeding and risk of triple-negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) study. International Journal of Cancer. 2018;142(11):2273. doi:10.1002/ijc.31258 Amant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer (2010) 46(18):3158–68. 10.1016/j.ejca.2010.09.010 Citation Format: Vaidarshi Abbagoni. Pregnancy-associated relapse of triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-04.

Abstract PO5-09-11: Abrupt involution of mouse mammary gland leads to inflammatory systemic changes along with mammary specific metabolic shifts that may enhance risk of breast cancer

Abstract Epidemiological data links higher parity and lack of breastfeeding with increased risk of breast cancer, specifically aggressive triple negative breast cancer (TNBC), and higher mortality rate. Following pregnancy and lactation, breast remodels to near pre-pregnancy stage through apoptotic cell death and adipocyte repopulation process. Long-term breastfeeding and gradual weaning of an infant leads to gradual involution (GI) of the breast, while lack of or abrupt discontinuation of breastfeeding after birth leads to abrupt involution (AI), when rapid and massive cell death takes place. Our studies have shown several precancerous changes, such as increased collagen deposition, inflammation, and hyperplasia in the mammary gland of mice after AI. However, the systemic impact of AI and how this increases risk of breast cancer is yet to be elucidated. Objectives: Our objective is to evaluate the systemic effects that are prompted by the AI mammary gland. We hypothesize that AI leads to marked alteration in lipid metabolism and systemic inflammation that enhances risk for breast cancer. Methods: FVB/n mice (8week old) were paired for breeding. At partum (day 0), dams were randomized to AI or GI cohort and standardized to 6 pups. AI mice had pups removed on day 7 postpartum (ppm) to mimic short-term breastfeeding. For GI mice 3 pups each were removed on day 28 and 31ppm to mimic gradual weaning. Tissues harvested on day 28, 56, and 120 postpartum. Body composition was measured by echo MRI. Glucose tolerance test (GTT) was performed after a 6 hour fast using a 2g/kg glucose intraperitoneal injection. Blood glucose was measured by glucometer. Serum insulin was analyzed by ELISA. HOMA-IR was calculated using blood glucose and serum insulin results. Serum was analyzed using multiplex ELISA by MesoScale Diagnostics. Mammary glands were subjected to untargeted lipidomics. Results: There were no significant differences in body weight, percent body fat or lean mass between AI and GI groups at any time point. However, at day 120 ppm (4 months after partum), we have observed significantly larger amount (1.29-fold increase) of perigonadal adipose tissue (visceral adipose) in AI mice than GI mice (p=0.0112; n=24-38/group). There were no significant differences in blood glucose, serum insulin, HOMA-IR, or GTT results between AI and GI groups at day 120. AI mice had significantly higher levels of cytokines IL-1β (3.1-fold increase, p=0.0417) and KC/GRO (1.5-fold increase, p=0.0196) than GI mice at day 120. At day 28, AI mammary glands had significantly higher amounts of level 3 identified oxidized ceramide containing sphingolipids that were linked to insulin resistance and diabetes. At day 56, GI mammary glands had significantly higher amounts of level 2 and 3 identified metabolites linked to cellular signaling and lipid metabolism. On day 120, there were no significant differences in lipid metabolites between groups. Conclusion: Although histologically GI and AI mammary glands return to near pre-pregnancy state within a month after partum, our data shows specific lipid changes in the AI mammary gland similar to what has been shown in women with TNBC. Furthermore, AI of the mammary gland leads to systemic effects on adiposity and inflammation that could be key to increased breast cancer risk. Further studies along these lines are in progress to understand the whole-body effects of AI and stratify preventive measures for women who cannot breast feed. Significance: Lack of breastfeeding is more prevalent in African American (AA) women and linked to higher risk of developing aggressive TNBC1. Our novel animal models of AI and GI help to link the impact of AI and systemic changes that may enhance breast cancer risk. In particular, we see an increase in visceral adiposity with AI. Understanding this mechanism will help identify strategies to reduce risk in women who are unable or choose not to breastfeed and ultimately help to reduce TNBC and TNBC-related mortality in AA women. Citation Format: Kate Ormiston, Kirti Kaul, Neelam Shinde, Djawed Bennouna, Rachel Kopec, Ramesh Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Abrupt involution of mouse mammary gland leads to inflammatory systemic changes along with mammary specific metabolic shifts that may enhance risk of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-11.

Abstract 2138: Understanding the link between breastfeeding and the risk of breast cancer through comparative analysis of the murine-based model of mammary gland involution

Abstract Introduction: A meta-analysis of 47 global epidemiological studies highlights a higher breast cancer risk in women who did not breastfeed or breastfed for a short time. Further studies showed this is especially true for triple-negative breast cancer (TNBC) patients. Premenopausal AA women (AAW) have a lower prevalence of breastfeeding and a higher incidence of TNBC and mortality. Our previous study compares short-term breastfeeding, abrupt involution (AI) with prolonged breastfeeding called gradual involution (GI), revealing that AI alone induces ductal hyperplasia four months postpartum. Our current investigation delves into early events during AI versus GI, employing a comprehensive approach encompassing histology, gene expression, and myeloid cell involvement. Methods: Utilizing FVB female mice, we conducted a comparative analysis of AI and GI. AI involved early pup removal, while GI was achieved through staggered weaning. The evaluation included analysis of histomorphology, gene/protein expression, and myeloid cell infiltration. Sequential mammary gland (MG) changes were monitored through H&amp;E staining, TUNEL assay, and DNA damage analysis. 3D-organoid cultures of luminal progenitors (LPs) were employed to assess the impact of AI versus GI. qRT-PCR, IHC, Western blot, and flow cytometry/multiplex imaging were employed for the differential expression analysis of molecular and cellular factors associated with AI/GI. Results: Our research showed that AI had early adipocyte repopulation, rapid cell death, DNA repair, and myeloid cell infiltration, resulting in a chronically inflamed microenvironment. In contrast, the GI triggers a controlled immune response and prolonged cell death, facilitating comprehensive remodeling of the MG. Our flow cytometric or multiplexing imaging analyses revealed that AI-affected glands exhibit an enrichment of CCL9-producing CD206+ M2-like macrophages and CD11b+Gr1+ myeloid-derived suppressor cells. Moreover, exogenous CCL9 treatment on LPs in 3D-organoid culture results in disorganized acinar-type organoids, mirroring morphological differences observed in LPs from AI mammary glands on day56 PPM. Further analysis of CCL9 treated organoids revealed the expansion of Esr1- LPs population in ex-vivo organoid culture which might indicate an increase in the putative cells of origin of TNBC. Conclusion: Our studies comparing AI and GI demonstrate that AI is producing a pro-tumorigenic environment in the breast. It is important to note that prolonged breastfeeding protects the breast, although this cannot be a singular risk factor for TNBC. Therefore, understanding the mechanism will lead to prevention strategies to improve outcomes for all women but, has the potential to have a significant benefit in AAW. Citation Format: Sanjay Mishra, Neelam Shinde, Maria Cuitino, Morgan Bauer, Dinesh Ahirwar, Vijaya Bharti, Kate Ormiston, Resham Mawalkar, Sara Alsammerai, Gautam Sarathy, Xiaoli Zhang, Anna Vilgelm, Ramesh Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Understanding the link between breastfeeding and the risk of breast cancer through comparative analysis of the murine-based model of mammary gland involution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2138.

Skin-to-Skin Contact and Breastfeeding After Planned Cesarean Birth Before and During the COVID-19 Pandemic.

Background: Benefits of early skin-to-skin contact (SSC) between mother and newborn are widely documented, including improved breastfeeding outcomes. While promoting immediate SSC is standard practice for vaginal birth, it happens less often after cesarean birth. It is not known how changes in hospital practices and staffing shortages during the COVID-19 pandemic have influenced the practice of SSC in the operating room (OR). This study aims to identify the relationship between SSC after cesarean birth and breastfeeding and compare SSC before and during the COVID-19 pandemic at a single institution. Materials and Methods: This was a retrospective cohort study of 244 subjects who had scheduled cesarean births during 2019 and 2020. The primary outcome was newborn feeding at hospital discharge. Secondary outcomes were time to initiate breastfeeding, newborn feeding at 4-8-weeks postpartum, and location of SSC initiation in 2019 versus 2020. Results: SSC within 3 days of birth was significantly associated with feeding type on discharge and/or 4-8 weeks postpartum. More subjects intending to exclusively breastfeed met this intention at discharge with SSC in the OR. Newborns who had SSC in the OR had significantly earlier initiation of breastfeeding. There was an increase in SSC in the OR between 2019 (27%) and 2020 (39%). Conclusion: SSC in the OR was associated with improved short-term breastfeeding outcomes in our study. If immediate SSC is not possible, SSC within 3 days of birth may have breastfeeding benefits. The increase in SSC in the OR during the COVID-19 pandemic indicates that SSC practices can be implemented, despite challenging circumstances.

Measures for the Prevention of Mother-to-Child Human T-Cell Leukemia Virus Type 1 Transmission in Japan: The Burdens of HTLV-1-Infected Mothers.

The main mode of mother-to-child transmission of the human T-cell leukemia virus (HTLV)-1 is through breastfeeding. Although the most reliable nutritional regimen to prevent HTLV-1 transmission is exclusive formula feeding, a recent meta-analysis revealed that short-term breastfeeding within 90 days does not increase the risk of infection. The protocol of the Japanese Health, Labor, and Welfare Science Research Group primarily recommended exclusive formula feeding for mothers who are positive for HTLV-1. However, there has been no quantitative research on the difficulties experienced by HTLV-1-positive mothers in carrying out these nutritional regimens, including the psychological burden. Therefore, this review was performed to clarify the burdens and difficulties encountered by mothers who are positive for HTLV-1; to this end, we analyzed the data registrants on the HTLV-1 career registration website "Carri-net" website. The data strongly suggest that it is not sufficient to simply recommend exclusive formula feeding or short-term breastfeeding as a means of preventing mother-to-child transmission; it is important for health care providers to understand that these nutritional regimens represent a major burden for pregnant women who are positive for HTLV-1 and to provide close support to ensure these women's health.

Breastfeeding initiation and duration among people with mild chronic hypertension: a secondary analysis of the Chronic Hypertension and Pregnancy trial

Increased duration of breastfeeding improves maternal cardiovascular health and may be especially beneficial in high-risk populations, such as those with chronic hypertension. Others have shown that individuals with hypertension are less likely to breastfeed, and there has been limited research aimed at supporting breastfeeding goals in this population. The impact of perinatal blood pressure control on breastfeeding outcomes among people with chronic hypertension is unknown. This study aimed to evaluate whether breastfeeding initiation and short-term duration assessed at the postpartum clinic visit differed according to perinatal blood pressure treatment strategy (targeting blood pressure <140/90 mm Hg vs reserving antihypertensive treatment for blood pressure ≥160/105 mm Hg). We performed a secondary analysis of the Chronic Hypertension and Pregnancy trial. This was an open-label, multicenter, randomized trial where pregnant participants with mild chronic hypertension were randomized to receive antihypertensive medications with goal blood pressure <140/90 mm Hg (active treatment) or deferredtreatment until blood pressure ≥160/105 mm Hg (control). The primary outcome was initiation and duration of breastfeeding, assessed at the postpartum clinic visit. We performed bivariate analyses and log-binomial and cumulative logit regression models, adjusting models for variables that were unbalanced in bivariate analyses. We performed additional analyses to explore the relationship between breastfeeding duration and blood pressure measurements at the postpartum visit. Of the 2408 participants from the Chronic Hypertension and Pregnancy trial, 1444 (60%) attended the postpartum study visit and provided breastfeeding information. Participants in the active treatment group had different body mass index class distribution and earlier gestational age at enrollment, and (by design) were more often discharged on antihypertensives. Breastfeeding outcomes did not differ significantly by treatment group. In the active and control treatment groups, 563 (77.5%) and 561 (78.1%) initiated breastfeeding, and mean durations of breastfeeding were 6.5±2.3and 6.3±2.1weeks, respectively. The probability of ever breastfeeding (adjusted relative risk, 0.99; 95% confidence interval, 0.93-1.05), current breastfeeding at postpartum visit (adjusted relative risk, 1.01; 95% confidence interval, 0.94-1.10), and weeks of breastfeeding (adjusted odds ratio, 0.87; 95% confidence interval, 0.68-1.12) did not differ by treatment group. Increased duration (≥2 vs <2 weeks) of breastfeeding was associated with slightly lower blood pressure measurements at the postpartum visit, but these differences were not significant in adjusted models. In a secondary analysis of the cohort of Chronic Hypertension and Pregnancy trial participants who attended the postpartum study visit and provided breastfeeding information (60% of original trial participants), breastfeeding outcomes did not differ significantly by treatment group. This suggests that maintaining goal blood pressure <140/90 mm Hg throughout the perinatal period is associated with neither harm nor benefit for short-term breastfeeding goals. Further study is needed to understand long-term breastfeeding outcomes among individuals with chronic hypertension and how to support this population in achieving their breastfeeding goals.

How Can We Prevent Mother-to-Child Transmission of HTLV-1?

The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a "silent disease" has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells; however, it is also responsible for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Most patients develop ATL as a result of HTLV-1 mother-to-child transmission. The primary route of mother-to-child transmission is through the mother's milk. In the absence of effective drug therapy, total artificial nutrition such as exclusive formula feeding is a reliable means of preventing mother-to-child transmission after birth, except for a small percentage of prenatal infections. A recent study found that the rate of mother-to-child transmission with short-term breastfeeding (within 90 days) did not exceed that of total artificial nutrition. Because these preventive measures are in exchange for the benefits of breastfeeding, clinical applications of antiretroviral drugs and immunotherapy with vaccines and neutralizing antibodies are urgently needed.

Short-Term breastfeeding and breastmilk supply changes associated with presence of systemic symptoms following COVID-19 vaccination among lactating individuals

Limited data exists on the experiences of lactating individuals after COVID-19 vaccination. We investigated the association of breastfeeding behaviors and breastmilk supply with the presence of systemic symptoms following COVID-19 vaccination.

Current Interventions to Prevent HTLV-1 Mother-to-Child Transmission and Their Effectiveness: A Systematic Review and Meta-Analysis.

Human T lymphotropic virus 1 (HTLV-1) may be transmitted from mother to child and affects at least 5-10 million individuals worldwide, with severe consequences on health. Strategies to prevent transmission are important, as there is no treatment or vaccine. This systematic review aimed to identify interventions to prevent HTLV-1 mother-to-child transmission and to determine their effectiveness. Exclusive formula feeding, short-term breastfeeding, use of freeze-thaw milk, milk pasteurization, maternal and infant antiretroviral drugs, caesarean section, early clamping of umbilical cord, screening of milk donors and avoidance of cross-breastfeeding were identified as possible strategies. Avoidance of breastfeeding is an intervention that prevents 85% of transmissions. This strategy is recommended in Japan, Brazil, Colombia, Canada, Chile, Uruguay, the USA and some regions of French Guyana. Whilst breastfeeding for &lt;3 months does not increase the risk of transmission compared to exclusive formula-feeding, concerns remain regarding the limited number of studies outside Japan, and the lack of information on women having higher risk of HTLV-1 transmission and on the ability of women to discontinue breastfeeding. Additional interventions are plausible, but data on their effectiveness are limited. The acceptance of interventions is high. These findings may guide healthcare professionals and support policymakers in implementing policies to avoid HTLV-1 mother-to-child transmission.

Abstract 5814: Lack of breast feeding may contribute to increased breast cancer risk by altering metabolism

Abstract Purpose: Epidemiological data links lack of breastfeeding with increased risk of breast cancer, particularly triple negative breast cancer (TNBC). The involution process is characterized by mammary tissue remodeling, including adipocyte repopulation and re-differentiation fueled by metabolic rewiring. Our mouse model mimicking short-term breast feeding that leads to abrupt involution (AI) revealed a chronic inflammatory state in the mammary gland (MG) (Basree, et al. Breast Cancer Research; 2019). As metabolic dysfunction is linked to increased BC risk, we sought to elucidate the effects of AI and gradual involution (GI) on MG energy metabolism and associated oxidative stress. In addition, we evaluated the impact of AI and GI on whole body glucose metabolism and insulin response/resistance. Methods: FVB/n mice (8week old) were paired for breeding. At partum, dams were randomized to AI or GI cohort and standardized to 6 pups per dam. AI mice had pups removed on postpartum day 7 (d7) to mimic short-term breastfeeding. GI mice had 3 pups removed on day 28 and 31 each to mimic gradual weaning. MGs were harvested on d28, 56, and 120 postpartum. Prior to harvest, mice underwent an echoMRI and insulin tolerance test (ITT). At harvest, mice were fasted for 4 hours, and blood was collected for serum insulin measurement using Ultra-Sensitive Insulin ELISA. Lipid peroxidation (MDA) and DNA adduct formation (8-OHdG), which represent chronic oxidative stress, were measured in MG by ELISA. Whole MG RNA were subjected to affymetrix followed by gene set enrichment analyses (GSEA) and qPCR for target validation. MGs were also subjected to untargeted metabolomics analysis and Mitofuel flex assay to assess substrate dependence by Seahorse Bioanalyzer. Results: GSEA and qPCR revealed enrichment of fatty acid oxidation (FAO) and mitochondrial oxidative phosphorylation (OXPHOS) pathways in AI MGs at d28, further validated by expression of genes (PGC-1α, Cpt-2, Srebp1c, and Chrebp). Metabolites associated with FAO were enriched in AI MGs at d28 and 56. Mitofuel flex assay indicated a significantly higher dependence on FAO in AI MGs. On d56, fasted blood glucose was significantly higher in AI mice with serum insulin and HOMA-IR trending to be higher than in GI mice. Level of 8-OHdG was elevated in AI MGs at d120. AI mice trended to be heavier, have greater body fat, and lower lean mass than GI Mice at d120. Body weight and percent body fat on d120 were positively correlated to MDA concentration in the mammary gland. Conclusion: Our mouse models of AI and GI revealed early MG specific metabolic shift towards increased FAO and OXPHOS that persists over time in AI glands. Similarly, increased oxidative stress and its association with adiposity at d120 indicates continued effect of AI. This change in adiposity, altered systemic glucose metabolism and metabolic shift seen in AI mice may contribute to the higher risk of breast cancer. [K.O. and K.K. are co-first authors.] Citation Format: Kate Ormiston, Kirti Kaul, Neelam Shinde, Allen Zhang, Morgan Bauer, Hee Kyung Kim, Ramesh K. Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Lack of breast feeding may contribute to increased breast cancer risk by altering metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5814.

Associations Between Postpartum Physical Symptoms and Breastfeeding Outcomes Among a Sample of U.S. Women 2-6 Months' Postpartum: A Cross-Sectional Study.

Objective: Postpartum urogynecologic and other physical symptoms are common and burdensome. Whether they interfere with breastfeeding has not been thoroughly examined, and this study aims to fill this gap. Methods: Mothers with an infant (2 to 6 months) were recruited from the U.S. ResearchMatch volunteer registry and completed the Life After Pregnancy Study, which assessed postpartum physical symptoms and breastfeeding self-efficacy, experiences, and problems. Modified Poisson regression and linear regression with fully conditional specification multiple imputation to handle missing data were used to examine the associations between physical symptoms and breastfeeding-related outcomes. Results: Among 222 participants, postpartum physical symptoms were common [e.g., painful sex (42%), urinary incontinence (32%)]. Breastfeeding problems were experienced by most participants [e.g., engorged breasts (72%), sore or cracked nipples (70%), breastfeeding or pumping was painful (67%)]. Although postpartum physical symptoms were not associated with breastfeeding for less than 2 months versus greater than/equal to 2 months (β = 0.94, 95% confidence interval [CI]: 0.78, 1.13), women with excess weight retention and those reporting painful sex or hemorrhoids were more likely to report breastfeeding problems such as sore or cracked nipples or perceived low milk supply. Overall, more physical symptoms were associated with more breastfeeding problems (adj β = 0.39, 95% CI: 0.17, 0.62) and lower breastfeeding self-efficacy (adj β = -2.24, 95% CI: -4.36, -0.13). Conclusions: Postpartum physical symptoms were associated with breastfeeding problems and overall poorer breastfeeding self-efficacy, but not with short-term breastfeeding duration. Future studies should explore how addressing physical symptoms among postpartum mothers might improve breastfeeding outcomes.

Mother-to-Child Transmission of Human T-Cell Leukemia Virus Type 1: Mechanisms and Nutritional Strategies for Prevention.

Simple SummaryMother-to-child transmission (MTCT) of human T-cell leukemia virus type 1 (HTLV-1) is a major cause of adult T-cell leukemia (ATL). Owing to the poor prognosis of ATL and the fact that more than one million people have been infected with this virus, the HTLV-1 antibody screening test was established in Japan in 2010 for all pregnant women to detect carriers and prevent MTCT. Because breastfeeding is the most common route of postnatal MTCT, exclusive formula feeding is widely used as a measure to prevent MTCT. Recently, it was reported that there is no obvious difference in the efficacy of short-term breastfeeding for ≤3 months in preventing MTCT compared to that in exclusive formula feeding, and that a duration of breastfeeding that does not exceed four months can be effective for preventing MTCT.Approximately 95% of mother-to-child transmission (MTCT) of human T-cell leukemia virus type-1 (HTLV-1) is derived from prolonged breastfeeding, which is a major cause of adult T-cell leukemia (ATL). Exclusive formula feeding (ExFF) is therefore generally used to prevent MTCT. A recent cohort study revealed that 55% of pregnant carriers chose short-term breastfeeding for ≤3 months in Japan. Our meta-analysis showed that there was no significant increase in the risk of MTCT when breastfeeding was carried out for ≤3 months compared with ExFF (pooled relative risk (RR), 0.72; 95% confidence interval (CI), 0.30–1.77), but there was an almost threefold increase in risk when breastfeeding was carried out for up to 6 months (pooled RR, 2.91; 95% CI, 1.69–5.03). Thus, short-term breastfeeding for ≤3 months may be useful in preventing MTCT. Breastmilk is the best nutritional source for infants, and any approach to minimizing MTCT by avoiding or limiting breastfeeding must be balanced against the impact on the child’s health and mother–child bonding. To minimize the need for nutritional interventions, it is necessary to identify factors that predispose children born to carrier mothers to MTCT and thereby predict MTCT development with a high degree of accuracy.

Childhood type 1 diabetes mellitus and risk factor of interactions between dietary cow’s milk intake and HLA-DR3/DR4 genotype

Short-term breastfeeding and early exposure to dairy products into infant diets, may be critical factors for development of type 1 diabetes. In this study, we investigate whether cow's milk proteins are risk factors for type 1 diabetes in genetically susceptible individuals (HLA DR3/DR4) by using statistical analysis and in silico approach. In order to verify the potential risk of the early introduction of cow's milk, we conducted this study to validate the veracity of this hypothesis in our population. We included 121 subjects, 55 type 1 diabetics and 74 controls from the region of Tlemcen (Algeria). Thus, the in silico approach was performed to determine the molecular mimicry region between Bovine serum albumin and beta-lactoglobulin with self-Islet antigen 2 and glutamate decarboxylase 65 by determining their sequences and their 3D structures. The risk factors associated with type 1 diabetes in a genetically predisposed individual (HLA DR3/DR4) retained by the logistic model are: type 1 and type 2 diabetes inheritance, the early introduction of cow's milk before 6 months and breastfeeding less than 9 months. Besides, the epitopes of cow’s milk proteins have the capacity to bind to predisposing HLA class II molecules (HLA DR3/DR4) and induce an immune reaction by the secretion of Interleukin 4 (Th2) and Interferon (Th1) which lead to the destruction of pancreatic beta cells. The early introduction of cow’s milk proteins in susceptible individuals is considered as risk factors for the pathogenesis of T1DM. The in silico approach confirm that BSA and BLG share sequence and structure homology with IA2 and GAD65. Communicated by Ramaswamy H. Sarma

The Effect of Early Postnatal Nutrition on Human T Cell Leukemia Virus Type 1 Mother-to-Child Transmission: A Systematic Review and Meta-Analysis.

The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen–thawed breast milk feeding (FTBMF) has been offered as an alternative method if breastfeeding is strongly desired. The aim of this review was to clarify the pooled risk ratio of MCTC of STBF and FTBMF compared with ExFF. This study was registered with PROSPERO (number 42018087317). A literature search of PubMed, CINAHL, the Cochrane Database, EMBASE, and Japanese databases through September 2018 identified 1979 articles, 10 of which met the inclusion criteria. Finally, 11 articles, including these 10 studies and the report of a recent Japanese national cohort study, were included in the meta-analysis. The pooled relative risks of STBF ≤3 months, STBF ≤6 months, and FTBMF compared with ExFF were 0.72 (95% confidence interval (CI): 0.30–1.77; p = 0.48), 2.91 (95% CI: 1.69–5.03; p = 0.0001), and 1.14 (95% CI: 0.20–6.50; p = 0.88), respectively. This meta-analysis showed no statistical difference in the risk of MTCT between STBF ≤3 months and ExFF, but the risk of MTCT significantly increased in STBF ≤6 months.

Issues of infant feeding for postnatal prevention of human T-cell leukemia/lymphoma virus type-1 mother-to-child transmission.

Nationwide antenatal human T-cell leukemia/lymphoma virus type-1 (HTLV-1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother-to-child transmission. Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV-1 antibodies. The mother-to-child transmission rate was calculated for each feeding option selected before birth. Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short-term breast-feeding (≤3months), exclusive formula feeding, frozen-thawed breast-milk feeding, and longer-term breast-feeding, respectively. Despite short-term breast-feeding, 8-18% of the mothers continued breast-feeding for 4-6months. The mother-to-child transmission rate with short-term breast-feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116-1.145). Because of the small number of children who were fed by frozen-thawed breast-milk, their mother-to-child transmission rate was not statistically reliable. Pregnant HTLV-1 carriers tended to select short-term breast-feeding in Japan. While short-term breast-feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother-to-child transmission because the vertical transmission rate with short-term breast-feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow-up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short-term breast-feeding and frozen-thawed breast-milk feeding.

Abstract PS17-28: Abrupt involution of lactating mammary gland induces metabolic reprogramming conducive to pro-tumorigenic changes

Abstract Background: Epidemiological studies indicate that prolonged breast feeding reduces the risk of triple negative breast cancer (TNBC), which carries the worst prognosis. Prolonged breastfeeding allows gradual involution (GI) of the breast while lack of or short-term breast feeding leads to abrupt involution (AI). We developed a novel murine model mimicking AI and GI of breast, and found that GI offers better protection to mammary glands from tissue remodeling associated injuries. Our data showed that AI leads to the development of pro-tumorigenic microenvironment and ductal hyperplasia1. Tissue remodeling involves orchestrated cell death and repopulation, and is closely associated with metabolic reprogramming from mitochondrial oxidative phosphorylation (OXPHOS) to glycolysis. Such metabolic alterations can contribute to cellular changes aiding malignant transformation2. We used our murine model to evaluate whether AI affects cellular metabolism differentially when compared to GI. Methods: Wild-type mice of FVB background were used in all our experiments. Twelve to fourteen week old uniparous mice were allowed to nurse (6 pups/dam) for 7 days postpartum. All pups were removed on day7 postpartum from the dams in AI cohort and three each on day28 and day31 from dams in GI cohort. Whole mammary glands and sorted luminal progenitor (LP) cells harvested on postpartum day28 were subjected to Affymetrix microarray analysis. Gene Set Enrichment Analysis (GSEA) was used to compute pathway enrichments in AI vs. GI glands. Differentially expressed genes were validated using qRT-PCR. Mammary glands harvested on day28 postpartum were subjected to mass spectrometry based untargeted metabolic profiling using Agilent QTOF. Raw data were analyzed using XCMS to assess key metabolic networks altered in AI vs GI glands. Targeted analysis for lactate, pyruvate, succinate and palmitic acid were performed using C13 labelled internal standards to compare OXPHOS vs glycolysis reliance in the AI and GI glands. Results: We observed enrichment of mitochondrial OXPHOS pathway, fatty acid metabolism and Myc target genes in both whole mammary gland and LP cells of AI vs. GI mice. Adipogenesis and hypoxia related genes were enriched in AI-glands. We observed significant upregulation of genes involved in glucose transport and fatty acid synthesis in AI glands, namely, Glut-5, Cidea, Acss2, Acsm3, Acly, Atp6v0d2, Acot11, and Elvol3. Several factors indicating a higher reliance on OXPHOS vs glycolysis, such as, Ppar-γ, Pgc1α, Cpt-2, Srebp1c and Chrebp were upregulated in AI glands. Upregulation of Cpt-2 and Srebp1c in the AI glands indicate higher flux through fatty acid oxidation and reliance on cholesterol synthesis. Metabolomic profiling revealed significant alteration in L-carnitine, GMP and XMP in AI glands which reflect mitochondrial fatty acid transport and nucleotide biosynthesis via guanine-guanosine salvage pathway. Pyruvate and lactate associated with glycolysis were increased in GI vs. AI glands. Conclusion: We show for the first time that in the abruptly involuting (AI) mammary glands following short-term breast feeding, there is a significant shift in the metabolic pathways towards mitochondrial OXPHOS and fatty acid oxidation compared to GI glands. Studies are underway to determine the effect of this metabolic shift on cellular transformation and tumorigenesis and the potential to target these pathways to reverse the detrimental effects of AI. 1. Basree MM, Shinde N, Koivisto C, et al. Breast Cancer Res. 2019; 21(1):80. 2. Ward PS, Thompson CB. Cancer Cell. 2012; 21(3):297. Citation Format: Neelam Shinde, Kirti Kaul, Allen Zhang, Saba Mehra, Resham Mawalkar, Hee Kyung Kim, Ramesh Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Abrupt involution of lactating mammary gland induces metabolic reprogramming conducive to pro-tumorigenic changes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-28.

Information Resource Network Analysis of Factors Influencing Breastfeeding Planning and Duration

This study aimed to identify the modifiable factors affecting breastfeeding planning and duration among healthy mothers and their use of breastfeeding information resources. A cross-sectional survey was conducted in a community setting. Four hundreds participants were recruited at five pediatric clinics and three community health centers located in Paju-si and Goyang-si, Gyeonggi-do, between January and May 2019. Based on the breastfeeding decision-making model, driven by Martens and Young's work, the survey items consisted of demographics, childbirth and breastfeeding characteristics, and breastfeeding information resources. In the analysis, 389 responses were used in the t-test, ANOVA, and logistic regression. Information resource networks were compared before and after childbirth including a subgroup analysis depending on the breastfeeding duration. The modifiable factors affecting breastfeeding planning and duration were antenatal and postpartum breastfeeding education and the provision of information in the hospital. The frequency of Internet use and websites visited were notable and potentially modifiable factors, which were also observed in the networks showing different relationship patterns according to participant subgroups and times. The childbirth event increased the centralization of the network in the planned group, while the network of the non-planned group was more diffused after childbirth. The network of the short-term breastfeeding group was characterized by a more centralized pattern and the resources of high betweenness centrality than the long-term group. Breastfeeding education is a consistent factor that affects breastfeeding behavior. A well-designed internet-based approach would be an effective nursing intervention to meet the needs of women seeking breastfeeding information and changing their behaviors.

A Nationwide Antenatal Human T-Cell Leukemia Virus Type-1 Antibody Screening in Japan.

Japan has been running a nationwide antenatal human T-cell leukemia virus type-1 (HTLV-1) antibody screening program since 2010 for the prevention of HTLV-1 mother-to-child transmission. As part of the program, pregnant women are invited to take an HTLV-1 antibody screening test, usually within the first 30 weeks of gestation, during regular pregnancy checkups. Pregnant women tested positive on the antibody screening test undergo a confirmatory test, either western blotting or line immunoassay. In indeterminate case, polymerase chain reaction (PCR) is used as a final test to diagnose infection. Pregnant women tested positive on a confirmatory or PCR test are identified as HTLV-1 carriers. As breastfeeding is a predominant route of postnatal HTLV-1 mother-to-child transmission, exclusive formula feeding is widely used as a postnatal preventive measure. Although there is insufficient evidence that short-term breastfeeding during ≤3 months does not increase the risk of mother-to-child transmission compared to exclusive formula feeding, this feeding method is considered if the mother is eager to breastfeed her child. However, it is important that mothers and family members fully understand that there is an increase in the risk of mother-to-child transmission when breastfeeding would be prolonged. As there are only a few clinical studies on the protective effect of frozen-thawed breastmilk feeding on mother-to-child transmission of HTLV-1, there is little evidence to recommend this feeding method. Further study on the protective effects of these feeding methods are needed. It is assumed that the risk of anxiety or depression may increase in the mothers who selected exclusive formula feeding or short-term breastfeeding. Thus, an adequate support and counseling for these mothers should be provided. In addition to raising public awareness of HTLV-1 infection, epidemiological data from the nationwide program needs to be collected and analyzed. In most cases, infected children are asymptomatic, and it is necessary to clarify how these children should be followed medically.

The impact of short-term predominate breastfeeding on cognitive outcome at 5 years.

Breastfeeding is associated with IQ, school attendance and income. Despite the known benefits of breastfeeding, the rate of exclusive breastfeeding up to 6months is low globally. We examined the effect of short-term breastfeeding on long-term IQ. In this secondary analysis of the prospective Cork BASELINE Birth Cohort Study, children were categorised as predominantly breastfed (n=288) versus exclusively formula-fed (n=254) at 2-months of age. Infants (n=404) receiving mixed feeding were excluded. Outcome was assessed using the KBIT-II at 5years. Multivariable linear regression was used to adjust for confounding variables. Following adjustment for confounding variables, children, predominately breastfed at 2months of age, demonstrated increased overall IQ (2.00 points (95% CI: 0.35 to 3.65); P=.018) and non-verbal IQ at 5years of age (1.88 points (95% CI: 0.22 to 3.54); P=.027) compared with those never breastfed. No significant relationship was found with verbal IQ (P=.154). A significant increase in composite and non-verbal IQ at 5years of age was associated with short-term breastfeeding. This study adds to a growing body of evidence that short-term breastfeeding promotes healthy cognitive development.