nutrients Article Osteopontin Levels in Human Milk Are Related to Maternal Nutrition and Infant Health and Growth Aysegül Aksan 1,2,3 , Izzet Erdal 4 , Siddika Songül Yalcin 4 , Jürgen Stein 3, * and Gülhan Samur 2   Citation: Aksan, A.; Erdal, I.; Yalcin, S.S.; Stein, J.; Samur, G. Osteopontin Levels in Human Milk Are Related to Maternal Nutrition and Infant Health and Growth. Nutrients 2021, 13, 2670. https://doi.org/10.3390/nu13082670 Academic Editor: Johannes B. van Goudoever Received: 5 July 2021 Accepted: 30 July 2021 Published: 31 July 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Institute of Nutritional Science, Justus-Liebig University, 35392 Giessen, Germany; ayseguel.aksan@ernaehrung.uni-giessen.de 2 Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Sihhiye, Ankara 06100, Turkey; gsamur@hacettepe.edu.tr 3 Institute of Pharmaceutical Chemistry, Goethe University, 60438 Frankfurt am Main, Germany 4 Department of Pediatrics, Faculty of Medicine, Hacettepe University, Altinda˘ g, Ankara 06230, Turkey; izzet.erdal@gmail.com (I.E.); siyalcin@hacettepe.edu.tr (S.S.Y.) * Correspondence: j.stein@em.uni-frankfurt.de Abstract: Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Meth- ods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smok- ing, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = −0.284, p = < 0.001; r = −0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = −0.450, p = < 0.001; r= −0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0–3 months and breast milk OPN levels (r = −0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated. Keywords: osteopontin; breast milk; human milk; mature milk; maternal diet; infant health; im- mune system 1. Introduction Breast milk is a unique source of nutrients that is physiologically tailored to meet the changing needs of the infant during the first six or more months of life [1–4]. In addition to providing optimal energy and nutrition, breast milk optimally manages the transition of the neonate to extrauterine life through a combination of bioactive proteins, lipids, oligosaccharides, and immunomodulatory components [5,6]. Epidemiological studies have shown that breastfed infants are less likely to develop necrotizing enterocolitis, leukemia, and lymphomas, infectious diseases and allergies, or immune-mediated diseases such as asthma, celiac disease, or diabetes, than infants un- able to be breastfed for a variety of reasons [6–9]. Furthermore, the intestinal microbiota of breastfed infants has been shown to differ from that of non-breastfed babies. Micro- bial dysbiosis in early life has been suggested to correlate with an increased incidence of immune-modulated disease such as asthma and atopic disease, obesity, and neurodevelop- mental disorders [7–10]. Infants fed breast milk have also been shown to have advantages with regard to cognitive development [11]. Nutrients 2021, 13, 2670. https://doi.org/10.3390/nu13082670 https://www.mdpi.com/journal/nutrients