lactoferrin and Premature-Birth

The aim of this systematic review was to report the role of lactoferrin supplementation for the prevention of preterm birth (PTB) in women at risk.. PubMed and Embase databases were searched. Inclusion criteria were studies exploring maternal and perinatal outcomes in women at high-risk for preterm birth receiving compared to those not receiving lactoferrin during pregnancy. The primary outcome was preterm PTB<37 weeks; the secondary outcomes were gestational age at birth, PTB<34 and 28 weeks, preterm premature rupture of the membranes (PPROM), chorioamnionitis and admission to Neonatal Intensive Care Unit. Random effect meta-analyses were used to analyze the data.. Six studies (333 pregnancies) were included. Overall, women taking lactoferrin had a lower risk of PTB<37 weeks of gestation with an OR of 0.43 (95% CI: 0.2-0.9). Likewise, gestational age at delivery was higher in women-taking compared to those not-taking lactoferrin (MD=0.46 weeks, SD=0.17, P=0.006). The other included studies explored the role of lactoferrin in affecting the inflammatory profile in the amniotic fluid of women undergoing invasive test, without reporting its actual role in preventing PTB.. Prophylactic administration of lactoferrin can reduce the risk of PTB in women at risk. Further large and adequately powered randomized trial are needed in order to elucidate the actual role of lactoferrin in reducing the risk of preterm birth and in affecting perinatal outcomes in women at risk.

Topics: Chorioamnionitis; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Lactoferrin; Pregnancy; Premature Birth

Prevention of preterm birth (PTB) is a global challenge and is one of the most important issues to be addressed in perinatal care. The hypothesis that ascending lower genital infection leads to PTB has been tested in numerous in vitro and in vivo studies. For patients with intractable vaginitis or high-risk patients with successive PTBs, mainly due to intra-uterine infection, the vaginal flora is enhanced to increase systemic immunity and locally propagate Lactobacillus species. It has been shown that the administration of lactoferrin (LF), a prebiotic with minimum side effects, may be effective in suppressing PTB. This hypothesis has been evaluated in this review using various relevant test examples. The findings suggest that LF may play a role in inflammatory protection in pregnant human cervical tissue. The antibacterial and anti-cytokine effects of LF in human-derived mucus-producing cervical cell lines were also demonstrated. It was also clarified that LF suppresses PTB and improves the prognosis of pups in inflammation-induced PTB animal models. Thus, we have identified that LF, a prebiotic contained in breast milk, can be clinically applied to suppress PTB in humans and to prevent PTBs in high-risk pregnancies.

Topics: Animals; Anti-Bacterial Agents; Female; Humans; Infant, Newborn; Lactoferrin; Pregnancy; Premature Birth; Vagina; Vaginosis, Bacterial

Early adverse fetal environments can significantly disturb central nervous system (CNS) development and subsequently alter brain maturation. Nutritional status is a major variable to be considered during development and increasing evidence links neonate and preterm infant impaired brain growth with neurological and psychiatric diseases in adulthood. Breastfeeding is one of the main components required for healthy newborn development due to the many "constitutive" elements breastmilk contains. Maternal intake of specific nutrients during lactation may alter milk composition, thus affecting newborn nutrition and, potentially, brain development. Lactoferrin (Lf) is a major protein present in colostrum and the main protein in human milk, which plays an important role in the benefits of breastfeeding during postnatal development. It has been demonstrated that Lf has antimicrobial, as well as anti-inflammatory properties, and is potentially able to reduce the incidence of sepsis and necrotizing enterocolitis (NEC), which are particularly frequent in premature births. The anti-inflammatory effects of Lf can reduce birth-related pathologies by decreasing the release of pro-inflammatory factors and inhibiting premature cervix maturation (also related to commensal microbiome abnormalities) that could contribute to disrupting brain development. Pre-clinical evidence shows that Lf protects the developing brain from neuronal injury, enhances brain connectivity and neurotrophin production, and decreases inflammation in models of perinatal inflammatory challenge, intrauterine growth restriction (IUGR) and neonatal hypoxia-ischemia (HI). In this context, Lf can provide nutritional support for brain development and cognition and prevent the origin of neuropsychiatric diseases later in life. In this narrative review, we consider the role of certain nutrients during neurodevelopment linking to the latest research on lactoferrin with respect to neonatology. We also discuss new evidence indicating that early neuroprotective pathways modulated by Lf could prevent neurodegeneration through anti-inflammatory and immunomodulatory processes.

Topics: Adult; Brain; Enterocolitis, Necrotizing; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Lactoferrin; Longevity; Milk, Human; Pregnancy; Premature Birth

Adverse pregnancy outcomes affect 54 million people globally per year, with at least 50% of these attributed to infection during gestation. These include inflammation of the membranes surrounding the growing fetus (chorioamnionitis), preterm prelabor rupture of membranes (PPROM), preterm birth (PTB), early-onset disease (EOD) and late-onset disease (LOD), neonatal and maternal sepsis, and maternal or fetal demise. Although universal screening and implementation of intrapartum antibiotic prophylaxis (IAP) has improved EOD outcomes, these interventions have not reduced the incidences of LOD or complications occurring early on during pregnancy such as PPROM and PTB. Thus, novel therapies are needed to prevent adverse pregnancy outcomes and to ameliorate disease risk in vulnerable populations. Lactoferrin has recently been explored as a potential therapeutic as it demonstrates strong antimicrobial and anti-biofilm activity. Lactoferrin is a glycoprotein capable of iron chelation found in a variety of human tissues and is produced in high concentrations in human breast milk. In recent studies, lactoferrin has shown promise inhibiting growth and biofilm formation of streptococcal species, including Group B Streptococcus (GBS), a prominent perinatal pathogen. Understanding the interactions between lactoferrin and GBS could elucidate a novel treatment strategy for adverse pregnancy outcomes caused by GBS infection.

Topics: Female; Humans; Infant, Newborn; Lactoferrin; Pregnancy; Premature Birth; Risk Factors; Streptococcal Infections; Streptococcus agalactiae

Streptococcal species are Gram-positive bacteria responsible for a variety of disease outcomes including pneumonia, meningitis, endocarditis, erysipelas, necrotizing fasciitis, periodontitis, skin and soft tissue infections, chorioamnionitis, premature rupture of membranes, preterm birth, and neonatal sepsis. In response to streptococcal infections, the host innate immune system deploys a repertoire of antimicrobial and immune modulating molecules. One important molecule that is produced in response to streptococcal infections is lactoferrin. Lactoferrin has antimicrobial properties including the ability to bind iron with high affinity and sequester this important nutrient from an invading pathogen. Additionally, lactoferrin has the capacity to alter the host inflammatory response and contribute to disease outcome. This Review presents the most recent published work that studies the interaction between the host innate immune protein lactoferrin and the invading pathogen,

Topics: Anti-Infective Agents; Female; Humans; Immunity; Infant, Newborn; Lactoferrin; Pregnancy; Premature Birth; Streptococcal Infections

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1-2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes.

Topics: Anemia; Anemia, Iron-Deficiency; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Female; Glycoproteins; Homeostasis; Humans; Inflammation; Iron; Lactoferrin; Oral Health; Pregnancy; Premature Birth; Protein Binding; Structure-Activity Relationship

Sepsis-related morbidity and mortality is an increasing concern in all neonatal ICUs (NICUs). Sepsis occurs in 20-40% of all preterm patients, and although much is known on the origin, the incidence is reported to be constantly increasing. Many risk factors account for the increased risk of sepsis in preterms, including use of broad-spectrum antibiotics selecting resistant microflora and pathogenic gut colonization, parenteral nutrition, acid inhibitors and steroids, as well as the systematic and long-lasting use of invasive management and in-dwelling lines. As treatment does not prevent severe long-term neurodevelopmental impairment and sequelae in septic premature neonates, the best strategy is to avoid infections rather than to treat them.. Published results from several recent randomized controlled trials currently show a level I evidence that fluconazole for prevention of fungal sepsis, probiotics for prevention of necrotizing enterocolitis, and bovine lactoferrin for prevention of bacterial sepsis should be considered as preventive strategies in NICUs.. In this article, the current evidence in favour of lactoferrin use in preterm neonates will be reviewed and the areas of further research and future improvements will be discussed in order to illustrate the implications of the recent findings for clinical practice or research.

Topics: Anti-Infective Agents; Chemoprevention; Enterocolitis, Necrotizing; Fluconazole; Humans; Infant, Newborn; Lactoferrin; Premature Birth; Probiotics; Randomized Controlled Trials as Topic; Sepsis

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Topics: Age of Onset; Animals; Anti-Infective Agents; Cattle; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lactoferrin; Premature Birth; Sepsis

Lactoferrin (LF) is a breast milk glycoprotein with protective effects against neonatal infections, mainly in premature and low-birth-weight (LBW) neonates. The aims of this study were to determine LF concentration in breast milk of mothers of LBW infants during the first 2 months postpartum, and to identify the factors associated with LF concentration.. Prospective study conducted as a part of an ongoing clinical trial in three Neonatal Units in Peru. We included 346 mothers of neonates with a birth weight <2000 g. We measured LF concentration in four stages of lactation using a commercial enzyme-linked immunosorbent assay kit. Multivariate analysis was performed to assess the association between maternal and neonatal factors, and LF concentration.. We collected 695 milk samples. LF mean concentration±standard deviation was 14.92±7.96 mg ml. LF concentration in breast milk of mothers of LBW infants was high and remained elevated even at 1 and 2 months postpartum. LF concentration in colostrum was higher in mothers with higher income and multiple pregnancies, and lower in mothers with peripartum infections.

Topics: Adult; Breast Feeding; Colostrum; Female; Humans; Income; Infant; Infant, Low Birth Weight; Infant, Newborn; Lactation; Lactoferrin; Linear Models; Male; Milk, Human; Multivariate Analysis; Peru; Postpartum Period; Pregnancy; Pregnancy, Multiple; Premature Birth; Prospective Studies; Young Adult

Lactoferrin (Lf) is an approximately 80-kDa iron-binding glycoprotein, belonging to the transferrin family, with well-known bacteriostatic and bactericidal properties. It is produced and stored in specific (secondary) neutrophil granules and released during neutrophil activation and degranulation. Nowadays, Lf has a well-known therapeutic indication for combating iron deficiency anemia (IDA) in pregnant women. Studies suggest that Lf plays an important role against cervicovaginal infections by decreasing cytokines levels, such as interleukin (IL)-6, in cervicovaginal fluid. The aim of this preliminary trial was to evaluate the effectiveness of Lf in preventing preterm delivery caused by cervical infections and ripening. From November 2009 to August 2010, 21 pregnant women (26-32 weeks pregnant), aged between 22 and 36 years, suffering from IDA, at risk of preterm delivery, were prospectively enrolled in the study. One group (N=14) received 100 mg of recombinant human lactoferrin (bLf) [corrected] (lattoferrina; AG-pharma) twice a day before meals, for one month. The other group (N=7) received 520 mg of ferrous sulfate (Ferro-Grad; Abbott Laboratories, USA) once a day. The patients underwent transvaginal ultrasound to evaluate cervical length and funneling, and vaginal swabs were used to detect infections and cervicovaginal fluid sample collection to determine IL-6 levels. The results showed a correlation between the oral administration of 200 mg of bLf [corrected] with both the normalization of vaginal flora (vaginal infection disappearance) and the decrease in IL-6 cervicovaginal fluid levels in women at risk of preterm delivery.

Topics: Administration, Oral; Adult; Anemia, Iron-Deficiency; Anti-Infective Agents; Cervix Mucus; Female; Ferrous Compounds; Gestational Age; Humans; Infant, Newborn; Interleukin-6; Lactoferrin; Pilot Projects; Pregnancy; Premature Birth; Prospective Studies; Recombinant Proteins; Ultrasonography; Vagina; Vaginal Smears; Vaginosis, Bacterial; Young Adult

Preterm delivery (PTD) occurs before the 37th week of gestation. Iron deficiency anemia and inflammatory processes either related to infection or sterile inflammatory response represent risk factors for PTD. Bovine lactoferrin (bLf), an emerging important regulator of iron and inflammatory homeostasis, can represent a new therapeutic approach for PTD treatment. Here an open-label cohort and subcohort study is reported. The cohort was designed to assess the effect of bLf oral administration on iron and inflammatory homeostasis in anemic pregnant women. The subcohort including women of the cohort with PTD threat was additionally treated with bLf intravaginal administration. A significant improvement of hematological parameters was observed in the women's cohort together with a consistent decrease of serum interleukin-6 (IL-6) levels. Combined administration of oral and intravaginal bLf to the women's subcohort with PTD threat decreased IL-6 in both serum and cervicovaginal fluids, cervicovaginal prostaglandin F(2α), and suppressed uterine contractility. BLf administration blocked further shortening of cervical length and the increase of fetal fibronectin thus prolonging the length of pregnancy. The deliveries occurred between the 37th and 38th week of gestation. These results provide strong evidence for a role of bLf in PTD treatment, thus extending the therapeutic potential of this multifunctional natural protein.

Topics: Administration, Intravaginal; Administration, Oral; Anemia, Iron-Deficiency; Animals; Cattle; Cervix Uteri; Dinoprost; Female; Humans; Immunologic Factors; Interleukin-6; Lactoferrin; Pregnancy; Pregnancy Complications; Premature Birth; Risk Factors; Treatment Outcome; Uterine Cervicitis

Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance.

Topics: Amniotic Fluid; Biomarkers; Female; Gestational Age; Humans; Infant, Newborn; Lactoferrin; Pregnancy; Premature Birth; Term Birth

To evaluate use of vaginal lactoferrin in prevention of preterm birth (PTB) in women with first trimester bacterial vaginosis and prior spontaneous PTB.. This is a retrospective cohort study of all consecutive singleton gestations with prior PTB, and first trimester diagnosis of bacterial vaginosis. Women who were found to have bacterial vaginosis were recommended lactoferrin 300 mg vaginal tablets daily for 21 days. The primary outcome was the incidence of PTB at less than 37 weeks of gestations. Outcomes were compared in women who received daily lactoferrin with those who did not.. During the study period, 847 pregnant women with prior spontaneous PTB were screened for bacterial vaginosis. Of them, 193 were found to have bacterial vaginosis in the first trimester, with an overall incidence of 22.8%. Out of the 193 women, 125 met the inclusion criteria for the study and were analyzed. Sixty of the included women received vaginal lactoferrin, while 65 did not. Women who received supplementation with lactoferrin had a significantly lower rate of PTB < 37 weeks (25.0 versus 44.6%;. Based on this small single-center retrospective study, supplementation with vaginal lactoferrin in women with first trimester bacterial vaginosis may be an option to reduce the risk of preterm delivery.

Topics: Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Lactoferrin; Pregnancy; Premature Birth; Retrospective Studies; Vaginosis, Bacterial

We previously reported that lactoferrin (LF) could be effective for preventing preterm delivery and intrauterine infections, based on data derived from mice and rabbits. Here we describe 6 women with a history of multiple pregnancy losses or preterm delivery and refractory bacterial vaginosis, who received prebiotic LF therapy and delivered an infant normally. Five of the women were pregnant and one was not at the time of this study. The Ethics Committee at Showa University Hospital and Showa University Koto Toyosu Hospital approved the therapeutic protocol. Vaginal suppositories and oral prebiotic LF were administered to patients who were refractory to conventional treatment for vaginosis and had a history of late miscarriages and very early preterm delivery due to refractory vaginitis and chorioamnionitis. LF significantly improved the vaginal bacterial flora. Lactobacillus, which was detectable in the vaginas of all patients after one month of LF therapy, gradually became dominant. The findings from these 6 patients suggest that administering LF to humans could help prevent refractory vaginitis, cervical inflammation, and preterm delivery.

Topics: Adult; Animals; Anti-Infective Agents; Bacteria; Drug Resistance, Bacterial; Female; Humans; Lactoferrin; Mice; Pregnancy; Premature Birth; Rabbits; Vagina; Vaginosis, Bacterial

There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-β2 (TGF-β2), α defensin 5 (HD5), β defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.

Topics: Colostrum; Defensins; Female; Gestational Age; Humans; Immunoglobulin A, Secretory; Immunologic Factors; Interferon-gamma; Interleukins; Lactation; Lactoferrin; Lipopolysaccharide Receptors; Milk, Human; Muramidase; Postpartum Period; Premature Birth; Solubility; Term Birth; Transforming Growth Factor beta2; Tumor Necrosis Factor-alpha

Background Lactoferrin (LF) is a highly represented, functional glycoprotein in human milk, exerting a wide range of anti-infective, immunomodulatory, and prebiotic actions in the neonate. Limited data are available assessing the concentrations and levels of LF in maternal milk over time during lactation in mothers who delivered infants at different GAs. Our aim with the present study was to determine the levels of LF in human milk from mothers of preterm and term infants and to evaluate the variations at a different time from delivery, in colostrum and mature milk. Methods Mothers of preterm and term infants from the Neonatology Unit in Foggia, Italy, were approached and enrolled in this study. From each mother, milk samples were collected within the first 3 days after birth (group A, 0-72 hours), between the 5th and 7th day after delivery (group B, 120-168 hours), and after the 10th day (group C, > 240 hours). All milk samples were divided into five groups, according to the GA of the infants: 24 to 27.6 weeks of GA (I), 28 to 31.6 weeks of GA (II), 32 to 34.6 weeks of GA (III), 35 to 37.6 weeks of GA (IV), and > 38 weeks of GA (V). Milk samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis to determine the content of LF. Results A total of 84 milk samples were collected from 28 mothers. We found that infant's GA, as well as the time of sampling, affected the levels of LF in milk. On one hand, LF showed higher content in human milk from group I (GA: 24-27.6 weeks) compared with the other groups (p < 0.01), and the levels of LF in colostrum were significantly correlated with GA (r = -0.31; p < 0.05). On the other hand, the LF content of milk had a significant decreasing trend over time. Overall, the highest values of LF were detected in preterm infants' maternal milk with a baby birth weight, lower than 1,400 g. Approximately 350 µg/mL was identified as the mean, physiological LF content in human mature milk in our population. Conclusions Levels of LF in human milk vary significantly over time during lactation and according to GA. This variability in the LF content of human milk may reflect the different needs of different infants during the early days and weeks of life. These data might help to inform models to design tailored supplementation strategies of LF in the nurseries and after home discharge.

Topics: Colostrum; Electrophoresis, Polyacrylamide Gel; Female; Gestational Age; Humans; Infant, Newborn; Italy; Lactation; Lactoferrin; Milk, Human; Premature Birth; Term Birth

Bioactive milk proteins may be important in protecting preterm infants from developing inflammation and necrotising enterocolitis (NEC). A preterm pig model was used to investigate the protective effects of enteral bovine lactoferrin (bLF) against NEC development and inflammation. Caesarean-delivered preterm pigs were fed parenteral and minimal enteral nutrition for the first 2 d followed by 2 d of total enteral nutrition before euthanasia. Pigs were stratified into two groups and fed with either a control formula (CON, n 15) or a 10 g/l of bLF-enriched formula (LF, n 13). NEC incidence, gut functions and inflammatory cytokines were analysed. NEC incidence and nutrient absorption were similar between the two groups. In pigs that developed NEC, disease outcome was more severe in the colon accompanied by increased intestinal permeability in LF pigs. In contrary, the LF pigs had a lowered IL-1β level in the proximal small intestine. Dose-dependent effects of bLF on cell proliferation, intracellular signalling and cytokine secretion were tested in porcine intestinal epithelial cells (PsIc1) in vitro. Low doses (0·1-1 g/l) increased cell proliferation via extracellular signal-regulated kinase (ERK), limited IL-8 secretion and prevented NF-κB and hypoxia-inducible factor-1α (HIF-1α) activation, suggesting anti-inflammatory effects. In contrast, at a higher dose (10 g/l), bLF exerted adverse effects by reducing cell proliferation, stimulating IL-8 release, inhibiting ERK activation and up-regulating NF-κB and HIF-1α activation. Overall, at a dose of 10 g/l, bLF exacerbated disease severity in pigs that developed NEC, while the in vitro studies indicated the positive effects of bLF at low doses (0·1-1 g/l). Supplementation of infant formulas with bLF should therefore be optimised carefully.

Topics: Animals; Blood Glucose; Cattle; Cell Proliferation; Cytokines; Enterocolitis, Necrotizing; Female; Gene Expression Regulation; Insulin; Intestinal Mucosa; Intestines; Lactoferrin; Lipopolysaccharides; Pregnancy; Premature Birth; Swine

Lactoferrin (LF) is one of the prebiotics present in the human body. A 38-year-old multiparous woman with poor obstetrical histories, three consecutive preterm premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was referred to our hospital. She was diagnosed as having refractory vaginitis. Although estriol vaginal tablets were used for 4 months, the vaginitis was not cured. We administrated vaginal tablets and oral agents of prebiotic LF, resulting in a Lactobacillus predominant vaginal flora. When she was pregnant, she continued to use the LF, and the Lactobacillus in the vaginal flora was continuously observed during pregnancy. An elective cesarean section was performed at the 38th week of pregnancy. When the administration of LF was discontinued after the delivery, Lactobacillus in the vaginal flora was disappeared.

Topics: Adult; Female; Fetal Membranes, Premature Rupture; Humans; Lactobacillus; Lactoferrin; Prebiotics; Pregnancy; Pregnancy Complications, Infectious; Premature Birth; Streptococcal Infections; Streptococcus agalactiae; Vagina; Vaginosis, Bacterial

To investigate the effect of recombinant human lactoferrin (rhLF) on cervical ripening using a rabbit model in which preterm labor was induced by bacterial endotoxin lipopolysaccharide (LPS).. Timed pregnant rabbits (New Zealand White, 3-4 kg, day 14) were randomly assigned to the following treatment groups: Group A, LPS + rhLF (n = 4); Group B, LPS (n = 4); and Group C, control (n = 4). Recombinant human lactoferrin (10 microg) was administrated to pregnant rabbits in Group A and not in Group B. Lipopolysaccharide (100 microg) was given to the rabbits in both groups for 3 days (days14-16). Drugs were administered as a vaginal suppository. On day 18, the rabbits were anesthetized with intramuscular ketamine hydrochloride (20 mg/kg) and diazepam (4 mg/kg). Both cervices of the rabbit uterus, which is bicorpus-bicolli, were taken out. One cervix was placed in 10% formalin solution for a histological study with standard hematoxylin-eosin staining. The other was used for an extension test to assess the grade of ripening. Extension was measured after a 5-mm length of cervical tissue was loaded with 5.8 g.. The histological study showed remarkably loose and edematous connective tissue in Group B cervices. Cervical tissues in Group A was not different from those in Group C. Extension lengths were 2.2 +/- 0.2 mm in Group A, 7.0 +/- 2.7 mm in Group B, and 1.7 +/- 0.3 mm in Group C.. These results suggest that rhLF inhibits cervical maturation induced by LPS in a rabbit model and may have a potential to prevent preterm delivery caused by cervical infection and ripening.

Topics: Administration, Intravaginal; Animals; Cervical Ripening; Cervix Uteri; Female; Humans; Lactoferrin; Lipopolysaccharides; Models, Animal; Pregnancy; Premature Birth; Rabbits; Random Allocation; Recombinant Proteins