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In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss.

A woman's nutritional status during pregnancy and breastfeeding is not only critical for her health, but also for that of future generations. Nutritional requirements during pregnancy differ considerably from those of non-pregnant women. Thus, a personalized approach to nutritional advice is recommended. Currently, some countries recommend routine supplementation for all pregnant women, while others recommend supplements only when necessary. Maternal physiological adaptations, as well as nutritional requirements during pregnancy and lactation, will be reviewed in the literature examining the impacts of dietary changes. All of these data have been studied deeply to facilitate a discussion on dietary supplement use and the recommended doses of nutrients during pregnancy and lactation. The aim of this review is to evaluate the knowledge in the scientific literature on the current recommendations for the intake of the most common micronutrients and omega-3 fatty acids during pregnancy and lactation in the United States, Canada, and Europe. Taking into account these considerations, we examine minerals, vitamins, and omega-3 fatty acid requirements. Finally, we conclude by discussing the potential benefits of each form of supplementation.

Pycnodysostosis, a rare autosomal recessive skeletal dysplasia, is caused by a deficiency of cathepsin K. Patients have impaired bone resorption in the presence of normal or increased numbers of multinucleated, but dysfunctional, osteoclasts. Cathepsin K degrades collagen type I and generates N-telopeptide (NTX) and the C-telopeptide (CTX) that can be quantified. Levels of these telopeptides are increased in lactating women and are associated with increased bone resorption. Nothing is known about the consequences of cathepsin K deficiency in lactating women. Here we present for the first time normalized blood and CTX measurements in a patient with pycnodysostosis, exclusively related to the lactation period. In vitro studies using osteoclasts derived from blood monocytes during lactation and after weaning further show consistent bone resorption before and after lactation. Increased expression of cathepsins L and S in osteoclasts derived from the lactating patient suggests that other proteinases could compensate for the lack of cathepsin K during the lactation period of pycnodysostosis patients.

Antimicrobial use in animals and the potential development of antimicrobial resistance is a global concern. So, non-antimicrobial techniques for animal disease control are needed. This study aimed to determine whether neonatal ceftiofur (CF) treatment affects piglet faecal microbiomes and whether faecal microbiome transplantation (FMT) can correct it. Two focal piglets per sow were assigned to treatments as follows: cffresh (n = 6) received CF (3 mg/kg intramuscular) at 7 d and fresh FMT at 13 d; cffrozen (n = 7) received CF at 7 d and frozen FMT at 13 d; CF (n = 8) received CF at 7 d and no FMT; and no CF (n = 5) received no CF or FMT. DNA was extracted from faecal samples collected on days 7, 13, and 18 for 16S rRNA amplicon analysis. All faecal blends used for the FMT consisted of pooled donor pig faeces at 1:2 ratio with saline, delivered orally at 3 mL/kg. Alpha and beta diversity metrics increased with age (p < 0.05). However, no effect of antibiotic or FMT treatment was evident in 13 and 18 d old piglets (p > 0.05). Although no effect of treatment was observed, information regarding microbial membership during lactation was gained.

Pregnancy and lactation are critical life stages with unique nutritional requirements, including for vitamin A (VA). Current DRIs for VA were published in 2001. The objective of this review was to identify and categorize evidence related to VA requirements in pregnancy and lactation since these DRIs were formulated. We searched MEDLINE and included articles according to an analytic framework of maternal VA exposure on status and health outcomes in the mother-child dyad. Intermediate and indirect evidence supports that maternal VA intakes can impact the mother's VA status, breastmilk, and health outcomes, as well as the child's VA status and select health outcomes. Food-based approaches can lead to more sustained, sufficient VA status in mothers and children. Research needs include further study linking maternal VA intakes on maternal and child VA status, and further associations with outcomes to determine intake requirements to optimize health.

Nipple pain and discomfort during or after breastfeeding remains one of the most common reasons for premature cessation of lactation among the affected women. The belief that yeasts, and especially Candida spp., are responsible for such symptoms is highly supported by many physicians, midwives, or lactation specialists, but is also viewed with scepticism by other health care providers. The aim of this paper is to provide an updated report of the evidence against, as well as in favour of, the "Candida hypothesis". Several studies have documented that lactating women with symptoms such as nipple soreness, with or without radiating breast pain, are more likely to test positive for Candida spp. than non-symptomatic women. However, its role as an undisputable aetiopathogenic factor for infection in these cases cannot always be established. Physicians should evaluate thoroughly such patients, because early and correct recognition of the underlying problem can prevent phenomena of early weaning.

Dedicated lactation rooms are a modern development as mothers return to work while still providing breastmilk to their absent infants. This study describes the built environment microbiome of lactation rooms and daycares, and explores the influence of temperature and humidity on the microbiome of lactation rooms. Sterile swabs were used to collect samples from five different sites in lactation rooms at University of California, Davis and from five different sites in daycares located in Davis, California. DNA from the swabs was extracted and the V4 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Temperature and relative humidity data were collected on a subset of the lactation rooms. Sampled lactation rooms could be either dedicated lactation rooms or could also serve other functions (e.g., combined lactation room and restroom lounge). The majority of sequence reads were identified as belonging to family Moraxellaceae, with 73% of all reads included in analysis identified as an unknown species of Acinetobacter. Alpha diversity was analyzed using the Shannon index, while beta diversity was analyzed using unweighted and weighted UniFrac distance. The Jaccard distance was used to measure amount of change at sampling locations between time points for analysis of the impact of temperature and humidity on the microbiome. There were significant differences in the beta diversity of the microbiome of lactation rooms by room type. There were also significant differences in the beta diversity of the microbiome by sample collection location. There were no significant differences in either alpha or beta diversity associated with room temperature or humidity. Additional studies are needed to understand if the differences in lactation room type may result in differences in the breastmilk microbiome of milk collected in those rooms, and to what extent any such differences may influence the infant microbiome.

Among the immunologically important bioactive factors present in human milk, lactoferrin (Lf) has emerged as a key player with wide-ranging features that directly and indirectly protect the neonate against infection caused by a variety of pathogens. The concentration of Lf in human milk is lactation-stage related; colostrum contains more than 5 g/L, which then significantly decreases to 2-3 g/L in mature milk. The milk of mothers who are breastfeeding for more than one year is of a standard value, containing macronutrients in a composition similar to that of human milk at later stages. The aim of this study was to evaluate lactoferrin concentration in prolonged lactation from the first to the 48th month postpartum. Lactating women (n = 120) up to 48 months postpartum were recruited to the study. The mean value of lactoferrin concentration was the lowest in the group of 1-12 months of lactation (3.39 ± 1.43 g/L), significantly increasing in the 13-18 months group (5.55 ± 4.00 g/L; p < 0.006), and remaining at a comparable level in the groups of 19-24 month and over 24 months (5.02 ± 2.97 and 4.90 ± 3.18 g/L, respectively). The concentration of lactoferrin in mother's milk also showed a positive correlation with protein concentration over lactation from the first to the 48th month (r = 0.3374; p = 0.0002). Our results demonstrate the high immunology potential of human milk during prolonged lactation and that Lf concentration is close to the Lf concentration in colostrum. Evidence of stable or rising immunoprotein levels during prolonged lactation provides an argument for foregoing weaning; however, breastfeeding must be combined with solid foods meet the new requirements of a rapidly growing six-month or older baby.

Human milk (HM) is the first dietary exposure in infancy and the best nutritional option for growth and healthy development of the newborn and infant. The concentrations of macronutrients, namely proteins, carbohydrates and lipids, change during lactation stages. HM has been studied extensively in the first 6 months of lactation, but there are limited data regarding milk composition beyond 1 or 2 years postpartum. The aim of our study was to describe longitudinal changes in HM macronutrient concentrations during the prolonged lactation of healthy mothers from the 1st to the 48th month. For the macronutrient content of milk of mothers breastfeeding for longer than 18 months, fat and protein increased and carbohydrates decreased significantly, compared with milk expressed by women breastfeeding up to 12 months. Moreover, the concentration of fat, protein and carbohydrates in HM over 2 years of lactation from the 24th to the 48th month remained at a stable level. However, analyzed macronutrients were positively (carbohydrate, r = 0.51) or negatively (fat, r = -0.36 and protein, r = -0.58) correlated with the amount of feeding. Our results create a greater potential for understanding the nutritional contribution of HM over 2 years of lactation and showed that the source of calories in breast milk for older children is mainly fat, while carbohydrates play a greater role in infant nutrition in the early stage. The observed changes of macronutrient concentrations from the 1st to the 48th month of lactation are probably related to the adaptation of milk composition to the increased energy demand of the intensively growing child.

Midwives and other health care providers face a dilemma when a pregnant woman develops a condition that usually is treated with a pharmacologic agent. Understanding of basic teratology associated with drugs as well as the FDA categorization of agents can assist professionals in recognizing which pharmaceuticals should be used or avoided. In addition to reviewing teratology, this article addresses the use of common drugs for the treatment of upper respiratory conditions, minor pain, gastrointestinal problems, psychiatric illnesses, and neurologic disorders. In each category, current evidence is presented pertaining to which agents should be recommended for pregnant women.

The composition of bioactive factors with immune activity in human breast milk is widely studied. However, the knowledge on rat milk immune factors during the whole lactation period is still scarce. This study aimed to analyze rat breast milk's immunoglobulin (Ig) content and some critical adipokines and growth factors throughout the lactation period, and to assess relationships with corresponding plasma levels. During lactation, milk concentration of the transforming growth factor (TGF)-β2 and -β3 showed a punctual increase in the first week, whereas adiponectin and leptin remained stable. In the second period of lactation (d14-21), despite the increase in the milk epidermal growth factor (EGF), a decrease in fibroblast growth factor 21 (FGF21) was detected at day 21. Milk IgA concentration had a progressive increase during lactation, while no significant changes were found in IgM and IgG. Regarding plasma levels, a decrease in all studied adipokines was observed in the second period of lactation, with the exception of IgA and TGF-β1, which reached their highest values at the end of the study. A positive correlation in IgM, IgG, and adipokine concentration was detected between milk and plasma compartments. In summary, the changes in the pattern of these bioactive compounds in rat milk and plasma and their relationships during lactation are established.

Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling.

Background: There is substantial evidence that postpartum prophylaxis with lithium lowers the rate of relapse in bipolar disorder. However, it is contraindicated during breastfeeding due to the high variability of the transfer into breast milk. Aims: We conducted a systematic review of the current evidence of studies assessing the transfer of lithium to lactating infants and short-term infant outcomes. Methods: An a priori protocol was designed based on PRISMA guidelines. Searches in PubMed and LactMed were conducted until September 2018. Studies assessing lithium pharmacokinetic parameters and short-term infant outcomes were included. Quality was assessed using a checklist based on international guidelines (i.e., FDA). Results: From 344 initial studies, 13 case reports/series with 39 mother-child dyads were included. Only 15% of studies complied with ≥50% of the items on the quality assessment checklist. Infants breastfeed a mean (SD) of 58.9 (83.3) days. Mean maternal lithium dose was 904 (293) mg/day, corresponding lithium plasma/serum concentration was 0.73(0.26) mEq/L, and breast milk concentration was 0.84(0.14) mEq/L. Mean infant lithium plasma/serum concentration was 0.23(0.26) mEq/L. Twenty-six (80%) infants had concentrations ≤0.30 mEq/L without adverse effects. Eight (20%) showed a transient adverse event (i.e., acute toxicity or thyroid alterations). All of them were also prenatally exposed to lithium monotherapy or polytherapy. Conclusion: The current evidence comes from studies with a degree of heterogeneity and of low-moderate quality. However, it identifies areas of improvement for future clinical lactation studies of lithium and provides support for some clinical recommendations.

Systemic inflammation is common in early lactation dairy cows and is associated with decreased milk production. The Scutellaria baicalensis plant contains flavonoids with anti-inflammatory and anti-oxidative properties, which may counteract the inflammatory state in early lactation dairy cows. The objective of this experiment was to determine whether Scutellaria baicalensis extract (SBE), a source of bioactive flavonoids, would alter the adaptation to lactation. Multiparous Holstein cows (n = 122) were used in a randomized block design to determine the effect of short-term and long-term postpartum administration of SBE on 305-d milk yield, 120-d milk component yield, and early lactation milk markers of inflammation and metabolic function. Treatments were 1) control, 2) short term (5-d) administration of the SBE (SBE5), and 3) long term (60-d) administration of the SBE (SBE60). Treatments were included in a treatment pellet that was identical to a control pellet in ingredient source and composition except for the extract (10 g/d SBE providing 3.3 g/d of the flavonoid baicalin), both provided via an automated milking system beginning on d 1 of lactation. Milk samples were collected on d 1, 3, and once during d 5-12 of lactation, followed by weekly sampling until 120 days in milk (DIM). Milk samples collected in the first 2 wk were used for biomarker analysis (haptoglobin, β-hydroxybutyrate [BHB], and glucose-6-phosphate [G6P]), and all samples were used for composition analysis. Cows were body condition scored every 2 wk prepartum and postpartum. Milk production, programmed pellet allocation, and actual provision of both pelleted feeds were recorded daily. Treatment effects were evaluated by contrasts between control and SBE5 and control and SBE60 for both the treatment (TP; wk 1-9) and carryover periods (CP; wk 10-37). Total pellet offered was greater for SBE60 in both the TP (P < 0.01) and CP (P = 0.02) but was not different for SBE5 during either period (P ≥ 0.13). No treatment effects were observed for body condition score (BCS), milk haptoglobin, BHB, or G6P. SBE5 did not alter milk yield or milk components. SBE60 increased whole-lactation milk yield by 1,419 kg (13%; P = 0.03). SBE60 increased milk lactose and fat yields (P ≤ 0.04) and tended to increase milk protein yield (P = 0.09) during TP, and each increased during CP (P ≤ 0.04). Somatic cell count decreased by 10% in SBE60 during TP (P = 0.02) but not CP (P = 0.13). Mastitis incidence tended to differ by treatment, being lesser for both SBE5 and SBE60 vs. control (14 and 15% vs. 33%). SBE supplementation did not impact time to pregnancy or hazard of leaving the herd. In conclusion, despite no detected treatment effects on BCS or milk biomarkers of inflammation and metabolic status, supplementation of postpartum dairy cows with Scutellaria baicalensis extract for 60 d was effective at increasing whole lactation milk yield.

Breast milk is essential for the initial development of neonatal animals, as it provides not only essential nutrients and a broad range of bioactive compounds but also commensal bacteria. The milk microbiota contributes to the "initial" intestinal microbiota of infants and also plays a crucial role in modulating and influencing neonatal health. However, the milk microbiota of sows has yet to be systematically investigated. The goal of the present study was to characterize variations in bacterial diversity and composition in sow milk over the duration of lactation using a high-throughput sequencing approach. Milk samples (n = 160) were collected from 20 healthy sows at eight different time points, and microbial profiles were analyzed by 16S ribosomal RNA (rRNA) sequencing using the Illumina MiSeq platform. The composition and diversity of the milk microbiota changed significantly in colostrum but was relatively stable in transitional and mature milk. Firmicutes and Proteobacteria were the most dominant phyla in sow milk. The relative abundances of the two most dominant bacterial genera, Corynebacterium and Streptococcus, were significantly higher in colostrum than in transitional milk and mature milk samples, and the other four most dominant bacterial taxa (Lactobacillus, two unclassified genera in the families Ruminococcaceae and Lachnospiraceae, and an unclassified genus in the order Clostridiales) demonstrated higher relative abundances in transitional and mature milk than in colostrum. Membrane transport, amino acid metabolism and carbohydrate metabolism were the most abundant functional categories in sow milk communities. Microbial network analysis based on the predominant genera revealed that the abundance of Helcococcus was negatively correlated with the abundances of most other genera in sow milk. Our results are the first to systematically indicate that the sow milk microbiota is a dynamic ecosystem in which changes mainly occur in the colostrum and remain generally stable throughout lactation.

Lactation in mammals is associated with a period of infertility, which serves to direct maternal metabolic resources toward caring for the newborn offspring rather than supporting another pregnancy. This lactational infertility is characterized by reduced pulsatile luteinizing hormone (LH) secretion and lack of ovulation. The mechanisms mediating suppression of LH secretion during lactation are unclear. There are potential roles for both hormonal cues such as prolactin and progesterone, and pup-derived cues such as suckling, on the inhibition of reproduction. To enable future studies using transgenic animals to investigate these mechanisms, in the present study our aim was to characterize lactational infertility in mice, and to investigate the effect of removing pup-derived cues on LH secretion, time to ovulation, and kisspeptin immunoreactivity. We first confirmed that C57BL/6J mice experience prolonged anestrus during lactation, which is dependent on establishment of lactation, as removal of pups the day of parturition led to immediate resumption of pulsatile LH secretion and normal estrous cycles. Once lactation is established, however, the lactational anestrus persisted for several days even after premature removal of pups. Pharmacological suppression of prolactin following premature weaning significantly reduced this period of lactational infertility. Progesterone does not appear to play a significant role in the suppression of fertility during lactation in mice, as levels measured during lactation were not different from nonpregnant mice. These data suggest that prolactin plays a key role in mediating anestrus during early lactation in mice, even in the absence of the suckling stimulus.

Mammary gland development occurs mainly after birth and is composed of three successive stages: puberty, pregnancy and lactation, and involution. These developmental stages are associated with major tissue remodeling, including extensive changes in mammary epithelium, as well as surrounding stroma. Three-dimensional (3D) mammary organoid culture has become an important tool in mammary gland biology and enabled invaluable discoveries on pubertal mammary branching morphogenesis and breast cancer. However, a suitable 3D organoid model recapitulating key aspects of lactation and involution has been missing. Here, we describe a robust and straightforward mouse mammary organoid system modeling lactation and involution-like process, which can be applied to study mechanisms of physiological mammary gland lactation and involution as well as pregnancy-associated breast cancer.

Human infants are born to breastfeed. While 50% of lactating persons struggle to make enough milk, there are no governmentally-approved drugs to enhance lactation1. Here, we engineer a variant of the naturally-occurring driver of lactation, the hormone Prolactin, to increase its serum half-life and produce a viable drug candidate. Our engineered variant, Prolactin-eXtra Long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. Our Prolactin-XL has a serum half-life of 70.9h in mice, 2,625-fold longer than endogenously active prolactin alone (70.9h v. 0.027h). We demonstrate that Prolactin-XL increases milk production and restores growth of pups fed by dams with pharmacologically-ablated lactation. We show that Prolactin-XL-enhanced lactation is accompanied by reversible, lactocyte-driven changes in mammary gland morphology. This work establishes long-acting prolactins as a potentially powerful pharmacologic means to combat insufficient lactation.

Hypothalamic magnocellular neurosecretory cells (MNCs) undergo dramatic structural reorganization during lactation in female rats that is thought to contribute to the pulsatile secretion of oxytocin critical for milk ejection. MNCs from male rats generate robust bursts of GABAergic synaptic currents, a subset of which are onset-synchronized between MNC pairs, but the functional role of the IPSC bursts is not known. To determine the physiological relevance of IPSC bursts, we compared MNCs from lactating and non-lactating female rats using whole-cell recordings in brain slices. We recorded a sixfold increase in the incidence of IPSC bursts in oxytocin (OT)-MNCs from lactating rats compared to non-lactating rats, whereas there was no change in IPSC bursts in vasopressin (VP)-MNCs. Synchronized bursts of IPSCs were observed in pairs of MNCs in slices from lactating rats. Our data indicate, therefore, that IPSC bursts are upregulated specifically in OT-MNCs during lactation, and may, therefore, contribute via rebound depolarization to the spike trains in OT neurons that lead to reflex milk ejection.