Browsing by Subject "Lactation"

Now showing 1 - 10 of 10
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    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
    (Mary Ann Liebert, Inc., 2021) Shere, Helen; Weijer, Laurel; Dashnow, Harriet; Moreno, L. Elizabeth; Foxworthy Scott, Susanna; Baker, Helen; Medicine, School of Medicine
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    Development of a Generic Physiologically-Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk
    (Wiley, 2022) Job, Kathleen M.; Dallmann, André; Parry, Samuel; Saade, George; Haas, David M.; Hughes, Brenna; Berens, Pamela; Chen, Jia-Yu; Fu, Christina; Humphrey, Kelsey; Hornik, Christoph; Balevic, Stephen; Zimmerman, Kanecia; Watt, Kevin; Obstetrics and Gynecology, School of Medicine
    Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1000 simulated women who were two days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.
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    Expansion of specialized epidermis induced by hormonal state and mechanical strain
    (Elsevier, 2015-05) Wu, Hsin-Jung; Easwaran, Teresa; Offutt, Carlos D.; Elgar, Richard Levi; Spandau, Dan F.; Koyama, Sachiko; Foley, John; Department of Medicine, IU School of Medicine
    In mammals, some sites of specialized skin such as the palms, soles, and lips grow proportionally with the animal. However, other types of specialized skin such as the nipple and anal/genital region are dramatically altered with changes of reproductive status. The specific cell types that mediate the growth of these sites have not been identified. In the mouse, we observed a dramatic expansion of the specialized epidermis of the nipple, coupled to changes in connective tissue and hair shaft density, which we designate as areola formation. During this process thymidine analog uptake was elevated in the epidermis and hair follicles. Although there were no changes in connective tissue cell proliferation, we did observe an altered expression of extracellular matrix genes. In addition, the fibroblasts of the virgin nipple areola and region showed increased transcript and protein levels for estrogen, progesterone, relaxin, and oxytocin relative to those of ventral skin. To determine the role of pregnancy, lactation hormonal milieu, and localized mechanical strain on areola formation, we created models that separated these stimuli and evaluated changes in gross structure, proliferation and protein expression. While modest increases of epidermal proliferation and remodeling of connective tissue occurred as a result of individual stimuli, areola formation required exposure to pregnancy hormones, as well as mechanical strain.
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    Hyperthyroidism in Pregnancy and Lactation: A Different Paradigm?
    (Oxford University Press, 2021-01-07) Rind, Jubran; Mariash, Cary N.; Medicine, School of Medicine
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    Lactation Duration and Long-Term Thyroid Function: A Study among Women with Gestational Diabetes
    (MDPI, 2018-07-21) Panuganti, Pranati L.; Hinkle, Stefanie N.; Rawal, Shristi; Grunnet, Louise G.; Lin, Yuan; Liu, Aiyi; Thuesen, Anne C.B.; Ley, Sylvia H.; Olesen, Sjurdur F.; Zhang, Cuilin; Epidemiology, School of Public Health
    Lactation is associated with reduced postpartum weight retention and a lower risk of several cardiometabolic disorders in population-based studies. We examined the association between lactation and long-term thyroid function among women with history of gestational diabetes mellitus (GDM), a high-risk population for subsequent metabolic complications. The study included 550 women who developed GDM in the Danish National Birth Cohort (1996⁻2002) and followed-up in the Diabetes & Women's Health Study (2012⁻2014). We assessed adjusted associations between cumulative lactation duration and concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) measured at follow-up. Women with longer cumulative lactation duration tended to have higher fT3 levels (adjusted β and 95% confidence interval (CI) for ≥12 months vs. none: 0.19 (0.03⁻0.36); p-trend = 0.05). When restricted to women with a single lifetime pregnancy to control for parity (n = 70), women who lactated for >6 months (vs. none) had higher fT3 levels (0.46 pmol/L (0.12⁻0.80); p-trend = 0.02) and a higher fT3:fT4 ratio (0.61 (0.17⁻1.05); p-trend = 0.007). Our findings suggested that a longer duration of lactation may be related to greater serum fT3 levels and fT3:fT4 ratio 9⁻16 years postpartum among Danish women with a history of GDM. The association was particularly pronounced among women who only had one lifetime pregnancy.
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    Multiscale imaging of basal cell dynamics in the functionally mature mammary gland
    (National Academy of Sciences, 2020-10-27) Stevenson, Alexander J.; Vanwalleghem, Gilles; Stewart, Teneale A.; Condon, Nicholas D.; Lloyd-Lewis, Bethan; Marino, Natascia; Putney, James W.; Scott, Ethan K.; Ewing, Adam D.; Davis, Felicity M.; Medicine, School of Medicine
    The mammary epithelium is indispensable for the continued survival of more than 5,000 mammalian species. For some, the volume of milk ejected in a single day exceeds their entire blood volume. Here, we unveil the spatiotemporal properties of physiological signals that orchestrate the ejection of milk from alveolar units and its passage along the mammary ductal network. Using quantitative, multidimensional imaging of mammary cell ensembles from GCaMP6 transgenic mice, we reveal how stimulus evoked Ca2+ oscillations couple to contractions in basal epithelial cells. Moreover, we show that Ca2+-dependent contractions generate the requisite force to physically deform the innermost layer of luminal cells, compelling them to discharge the fluid that they produced and housed. Through the collective action of thousands of these biological positive-displacement pumps, each linked to a contractile ductal network, milk begins its passage toward the dependent neonate, seconds after the command.
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    PDK regulated Warburg effect protects differentiated adipocytes against ROS
    (2014-10-06) Roell, William Christopher; March, Keith L.; Considine, Robert V.; Harris, Robert A.; Tune, Johnathan David
    Literature has demonstrated the ability of human adipose tissue to generate large amounts of lactate. However, it is not understood why adipose tissue produces lactate, how the production of lactate is regulated, and what potential benefit this has to the adipocyte or the organism. We first characterized a human model of adipogenic differentiation with minimal donor to donor variability to assess metabolic changes associated with mature adipocytes compared to their precursors. Indeed, similar to what was observed in human clinical studies, the differentiated adipocytes demonstrated increased lactate production. However, the differentiated adipocytes compared to their precursors (preadipocytes or ASCs) demonstrate an aerobic glycolysis-like (also called Warburg effect-like) increase in glycolysis characterized by a 5.2 fold increase in lactate production in normoxic conditions (atmospheric oxygen tension). Remarkably, this increase in lactate occurred even though the differentiated adipocytes simultaneously demonstrate an increase in oxidative capacity. This low fraction of oxidative capacity coupled with increased lactate production indicated regulation of oxidative rates most likely at the point of pyruvate conversion to either acetyl-CoA (oxidative metabolism) or lactate (glycolytic metabolism). To investigate the potential regulation of this metabolic phenotype, PDK isoform expression was assessed and we found PDK 1 and 4 transcript and protein elevated in the differentiated cells. Non-selective pharmacologic inhibition of the PDKs resulted in decreased lactate production, supporting a regulatory role for PDK in modulation of the observed Warburg effect. PDK inhibition also resulted in increased ROS production in the adipocytes after several hours of treatment and a decrease in cell viability when PDK inhibition was carried out over 36 hours. The resulting loss in viability could be rescued by antioxidant (Tempol) treatment, indicating the decrease in viability was ROS mediated. Similar to what is seen in cancer cells, our data demonstrate that differentiation of human adipocytes is accompanied by a PDK-dependent increase in glycolytic metabolism (Warburg effect) that not only leads to lactate production, but also seems to protect the cells from increased and detrimental generation of ROS.
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    The MPRINT Hub Data, Model, Knowledge and Research Coordination Center: Bridging the gap in maternal-pediatric therapeutics research through data integration and pharmacometrics
    (Wiley, 2023) Quinney, Sara K.; Bies, Robert R.; Grannis, Shaun J.; Bartlett, Christopher W.; Mendonca, Eneida; Rogerson, Colin M.; Backes, Carl H.; Shah, Dhaval K.; Tillman, Emma M.; Costantine, Maged M.; Aruldhas, Blessed W.; Allam, Reva; Grant, Amelia; Abbasi, Mohammed Yaseen; Kandasamy, Murugesh; Zang, Yong; Wang, Lei; Shendre, Aditi; Li, Lang; Obstetrics and Gynecology, School of Medicine
    Maternal and pediatric populations have historically been considered "therapeutic orphans" due to their limited inclusion in clinical trials. Physiologic changes during pregnancy and lactation and growth and maturation of children alter pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Precision therapy in these populations requires knowledge of these effects. Efforts to enhance maternal and pediatric participation in clinical studies have increased over the past few decades. However, studies supporting precision therapeutics in these populations are often small and, in isolation, may have limited impact. Integration of data from various studies, for example through physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling or bioinformatics approaches, can augment the value of data from these studies, and help identify gaps in understanding. To catalyze research in maternal and pediatric precision therapeutics, the Obstetric and Pediatric Pharmacology and Therapeutics Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Maternal and Pediatric Precision in Therapeutics (MPRINT) Hub. Herein, we provide an overview of the status of maternal-pediatric therapeutics research and introduce the Indiana University-Ohio State University MPRINT Hub Data, Model, Knowledge and Research Coordination Center (DMKRCC), which aims to facilitate research in maternal and pediatric precision therapeutics through the integration and assessment of existing knowledge, supporting pharmacometrics and clinical trials design, development of new real-world evidence resources, educational initiatives, and building collaborations among public and private partners, including other NICHD-funded networks. By fostering use of existing data and resources, the DMKRCC will identify critical gaps in knowledge and support efforts to overcome these gaps to enhance maternal-pediatric precision therapeutics.
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    Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women
    (Mary Ann Liebert, 2017-12) Lee, Sun Y.; McCarthy, Alicia M.; Stohl, Hindi; Ibrahim, Sherrine; Jeong, Christina; Braverman, Lewis E.; Ma, Wendy; He, Xuemei; Mestman, Jorge H.; Schuller, Kristin E.; Jahreis, Katherine A.; Pearce, Elizabeth N.; Leung, Angela M.; Obstetrics and Gynecology, School of Medicine
    Background: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 μg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. Methods: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 μg/L. Results: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 μg/L, 3.1 μg/L, and 514 μg/L, respectively. One-third of women had UIC <100 μg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 μg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. Conclusion: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 μg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants.