Immunologic aspects of breast feeding, antiinfectious activity of breast milk.

The most apparent immunologic role of the mammary gland is supply to antibodies to the neonate. In cattle the gland must be able to secrete large quantities of IgG antibodies over a short time period to supply the offspring with protection against systemic pathogens. This is accomplished by selective transfer of IgG from serum to the gland followed by eventual absorption by the neonate gut. In all mammals, the mammary glands provide IgA antibodies specific for pathogens or antigens which enter or invade the neonatal gut. An entero-mammary cell circulation provides the mechanism for conveying such specificity to the lacteal IgA antibodies. Some IgA antibodies may also be derived from the circulation so that the quantitative significance of serum derived versus locally produced IgA in different species requires clarifications. IgG and IgG lacteal antibodies ingested by the neonate, provide short-term systemic and long-term enteric humoral immunity to the neonate. In addition to providing passive immunity, at least swine IgG appears to have a regulatory role in the development of the systemic humoral immune system of the neonate. Such a phenomenon may be general for IgG antibodies transferred in colostrum or in utero. While passive antibodies and immunoglobulins may be most important for the neonate, the many other potentially anti-infectious elements transferred in colostrum and milk may also play important roles. 'Bifidus' factor particularly, but also lysozyme and lactoferrin are probably all important although more convincing experimental data will be needed to support this assumption. Studies of cells of the lymphoid and reticuloendothelial systems in milk are more recent and their role in the neonate remains to be convincingly demonstrated. In summary, the immunologic and anti-infectious roles of the mammary glands are (1) Supply of IgA antibodies against enteric antigens to the neonate on a 'long-term' basis throughout lactation; (2) Short-term supply of IgG (and IgA) in Group II and III mammals for eventual absorption into neonatal serum; (3) The supply of numerous nonspecific factors such as 'bifidus factor,' lactoferrin, and lysozyme throughout lactation; (4) Regulation of the development of humoral immunity by an apparent feedback mechanism involving maternal IgG; (5) Self-protection of the gland by sensitized T-lymphocytes acting directly or using lymphokines on macrophages; and (6) Self-protection of the gland by secreted antibodies that may act in complement-independent cytolysis, as opsoins for polymorphonuclear-leukocytes or directly as agents preventing colonization.     

Type-specific antiviral antibodies to genital human papillomavirus types in mothers and newborns

Type-specific antibodies to human papillomaviruses (HPVs) can be detected in most infected adult patients, and they have virus-neutralizing properties. However, there is a dearth of information on the seroprevalence of maternal and neonatal antibodies to HPV capsid antigens. Sera from 104 mothers, their newborns, and 3 twin pregnancies were analyzed by an enzyme-linked immunosorbent assay (ELISA) for the presence of specific IgG, IgM, and IgA antibodies to virus-like particles of HPV-6, -11, -16, -18, and -31. Maternal IgG positivity rates to HPV types 6, 11, 16, 18, and 31 were 23.1%, 2.9%, 8.7%, 5.8%, and 9.6%, respectively. Neonatal rates did not differ significantly, and individual IgG ELISA values of mothers and their infants and all paired twins showed a very high correlation. In contrast, nearly all IgM and IgA individual values in newborns were designated negative, whereas mothers' positivity rates ranged as high as 19.2%. Infants showed no HPV-related lesions at birth or at 4-year follow-up. Seven of 8 tested children lost IgG HPV antibodies in a follow-up examination. Similar anti-HPV IgG seropositivity in mothers and newborns and a lack of neonatal IgA and IgM together with twin and follow-up results indicate that neonatal IgG is not a sign of intrauterine HPV infection but, rather, maternofetal antibody transmission.     

The effects of norgestrel, ethinyl estradiol, and their combination, Ovral, on lactation and the offspring of rats treated during lactation

This report considers the effects of Ovral and its estrogenic and pr ogestational components on lactation and the offspring of rats treated during lactation. Ovral contains .5 mg of norgestrel and .05 mg of ethinyl estradiol and in rats represents 10 mcg per kg of the progestogen and 1 mcg per kg of the estrogen. In this study these doses and 5 and 25 multiples were employed singly and in combinations maintaining a 10 to 1 ratio. Lactation females were treated by gavage with the drugs dissolved in corn oil. There were suitable controls. 60 lactating rats were treated, beginning on day of delivery and continuing for 21 days, with one of 9 different dosage schedules. Each litter was reduced to 6, 3 males and 3 females. The mothers were sacrificed on Day 22. The young were sacrificed at the age of 6 weeks. The highest mortality of the young was due to cannibalism but the incidence of this was apparently not due to the drug treatment. Drug treatment had no eff ect on survival of the young or on their growth weights. Growth weights of various organs were not affected. Data suggest that no biologically important amounts of these drugs are secreted in the milk when they are administered to lactating mothers at 1, 5, or 25-fold multiples of the clinical dose. No significant effects were seen on the bodies or on any of the organ weights of the mothers sacrificed at the time of weaning the young.     

初乳中丙型肝炎病毒标志物的测定

目的：检测乳汁中丙型肝炎病毒（ＨＣＶ）标志物，探讨丙型肝炎病毒通过母乳传播的可能性。方法：用间接酶联免疫吸附试验同时检测血清和初乳中抗ＨＣＶ－ＩｇＧ、ＩｇＡ、ＩｇＭ３类抗体；并用逆转录聚合酶链反应检测ＨＣＶＲＮＡ。结果：在血清抗ＨＣＶ－ＩｇＧ阳性的３５例产妇初乳标本中，抗ＨＣＶ－ＩｇＡ、ＩｇＧ、ＩｇＭ抗体分别检出１９例、６例及１例。ＨＣＶＲＮＡ在３５份血清中阳性检出率为４０．０％（１４／３５），而初乳中仅检出２例（５．７％；２／３５），两者之间有明显差异（Ｐ＜０．０１）。结论：血清抗ＨＣＶ－ＩｇＧ阳性产妇初乳中的抗ＨＣＶ抗体以ＩｇＡ类为主；血清中ＨＣＶＲＮＡ的检出率明显高于初乳。血清抗ＨＣＶ－ＩｇＧ阳性的产妇，尤其是初乳中抗ＨＣＶ－ＩｇＡ和ＨＣＶＲＮＡ也为阳性者，有可能通过哺乳而导致婴儿感染ＨＣＶ。     

Maternal anemia induces changes in immunological and nutritional components of breast milk

Abstract

Objective: The effects of low maternal hemoglobin levels on the immunological and nutritional components of breast milk at different maturation stages were investigated.

Methods: Colostrum, transitional and mature milk were collected from 25 mothers with normal hemoglobin levels (control group) and 18 mothers with hemoglobin levels below 11?g/dL (anemia group). Total protein, antibodies, complement proteins, fat and calorie, lipase, iron, transferrin levels, total iron-binding capacity, latent iron-binding capacity (LIBC) and transferrin saturation index (TSI) were determined.

Results: In contrast to the control group, anemic mothers had higher total protein levels in milk, lower IgA and IgG levels in colostrum, lower C3 protein levels in milk, lower C4 protein levels in colostrum and transitional milk, higher fat in the colostrum and lower calorie content in mature milk. In both groups, lipase was lower in mature milk and iron concentration was similar. Transitional and mature milk from anemic mothers had higher LIBC and lower TSI values.

Conclusion: A decrease in maternal hemoglobin levels causes immunological and nutritional alterations in milk at different maturation stages. Special measures must therefore be taken for mothers at risk of developing anemia to ensure they can provide high-quality milk to their babies.     

Passage of zona antibodies via placenta and milk following active immunization of female mice with porcine zonae pellucidae

Female mice heteroimmunized with heat-solubilized porcine zonae produced a significant antibody response to this immunogen as measured by radioimmunoassay (RIA) but their fertility was unaffected and normal litters were delivered. Monitoring for anti-zonae pellucidae activity in the sera of offspring from such immunized mothers by RIA indicated that the zonae antibodies were transferred from mother to young via the placenta and milk. Such transferred antibodies cross-reacted with and bound to the zonae of female offspring as demonstrated by immunofluorescent techniques. These data are significant to the future consideration of use of specific zona antigens for development of a contraceptive vaccine.     

Detection of antisperm antibodies: their localization to human sperm antigens that are transferred to the surface of zona-free hamster oocytes during the sperm penetration assay

The authors have developed an extension of the sperm penetration assay for detecting serum immunoglobulins to sperm antigens that are transferred to the plasma membrane of a sperm-penetrated hamster oocyte. After the hamster oocytes have been scored for sperm penetration by observing for the presence of swollen sperm heads, they are incubated in serum followed by either a 20-minute treatment with rhodamine-conjugated protein A (which binds to most subclasses of IgA, IgG, and IgM) or a 2-hour incubation in guinea pig serum (complement). Positive fluorescence indicates that the serum contains antibodies to sperm antigens that were transferred to the surface of an oocyte during gamete fusion. Complement-mediated lysis indicates that the immunoglobulin that is bound can also fix complement. The advantages of this assay for detection of serum antisperm antibodies are that it is an extension of a widely used assay, is rapid and requires readily available reagents and equipment, can detect most subclasses of IgA, IgG, and IgM, detects antibodies to those sperm antigens that may be transferred to the oocyte during fertilization, and indicates whether the detected antisperm antibodies can mediate complement-dependent lysis of the fertilized oocyte.     

Detection of autoimmunity to sperm: mixed antiglobulin reaction (MAR) test or sperm agglutination? A study on 537 men from infertile couples

Two different ways of testing for antisperm antibodies were compared: the mixed antiglobulin reaction (MAR) test for demonstration of antibodies of the IgG and IgA classes bound in vivo to the sperm membrane antigens and the gelatin agglutination test for detection of nonbound antisperm antibodies in serum and seminal plasma. Samples from 537 men from infertile couples were investigated. Antibodies bound to the sperm membrane were detected in 49 men (9.1%), IgG in 44 (8.2%), and IgA in 38 cases (7.1%). Sperm agglutinins were recorded in seminal plasma from 30 men (5.6%) and in serum (titer greater than or equal to 16) from 43 men (8.0%). The investigation revealed a very close correlation between the results of MAR testing and the occurrence of sperm agglutinins in serum and seminal plasma. However, if one focuses on antisperm antibodies of the IgA class, which seem to play the major role in male immune infertility, the MAR test offered the advantage that a minor group of patients with pure IgG responses could be distinguished, and rare cases with mainly or exclusively locally produced IgA antibodies could be detected.     

The effects of oral contraceptive use on iron and copper concentrations in breast milk.

OBJECTIVE: To determine the effects of oral contraceptive (OC) treatment on maternal iron and copper metabolism during lactation. DESIGN: Observational study. SETTING: Private and public clinics in Brazil. PATIENT(S): Lactating mothers attending the family planning clinic of the University of Brasilia. INTERVENTION(S): The OCs used were a combination pill (0.15 mg of levonorgestrel and 0.03 mg of ethinyl estradiol) and a minipill (0.35 mg of norethidrone). Blood and breast milk samples were collected before and after a measured period of OC treatment. MAIN OUTCOME MEASURE(S): Iron and copper concentrations were studied in the serum and breast milk of 54 breast-feeding mothers who had been advised by their physicians to use an OC, and in a control group. RESULT(S): Regression analysis was performed using a model that took into consideration socioeconomic status, number of children, duration of previous lactation, type of OC, length of treatment, and age. Repeated measurements (before and after OC treatment) showed that only copper concentrations in breast milk were significantly affected by stage of lactation. During the study period, which varied from 2-15 weeks, the decline in iron concentrations in breast milk was negligible, whereas copper concentrations decreased by 50%. CONCLUSION(S): The use of OCs does not appear to affect significantly the secretion of iron and copper in breast milk during the first 6 months of lactation.     

Debate on the use of hormonal contraceptives during lactation

Contraceptive steroids taken during the lactation period will, in small measure, be transferred to the milk. The side effects from estrogens administered during lactation are enough to contraindicate their use at this time. Low-dose gestagens are sufficient to achieve contraceptive effect. A study of 6-7-year-old children whose mothers took OCs (oral contraceptives) during lactation is being conducted currently to ascertain longterm side effects or possible effects outside the hypothalamic-pituitary-gonadal axis. However, at this time the minipill of 30 mcg d-norgestrel daily is considered safe for a nursing mother and her baby.     

Immunoperoxidase assay for detection of specific IgG and IgA antibodies to human spermatozoa in infertile women

A new immunoperoxidase antibody-membrane antigen (IPAMA) technique for the detection of IgG and IgA antibodies specific for sperm antigens is described. The technique utilizes as antigen sperm cells dried on glass slides and stored at -70 degrees C. Sera of 82 infertile women, 50 primiparas, 50 multiparas and 25 children were tested by IPAMA. Results obtained with the IPAMA test for sperm-specific IgG are compared with the results obtained by the sperm immobilization test (SIT). By the IPAMA technique, 11 of 82 infertile women (13.4%) were positive for sperm-specific IgG antibodies, 12 (14.6%) for IgA antibodies and three (3.7%) for both. In the control groups only two of 125 subjects were positive for sperm-specific IgG and none for IgA antibodies. The difference in the prevalence of anti-sperm antibodies between the control groups and the infertility group was highly significant (P less than 0.001). There was agreement between the results of the IPAMA and SIT as to the presence or absence of antibodies in seven of the 11 IgG-positive sera in the infertility group. Four more sera were IgG positive by IPAMA only. The two positive sera in the control group were detected by both IPAMA and SIT. Since the IPAMA technique is simple, does not require special equipment and utilizes stored antigen, it seems that this method could be useful in mass screening of infertile couples.     

Immunogenicity of a multi-component recombinant human acrosomal protein vaccine in female Macaca fascicularis

A vaccine formula comprised of five recombinant human intra-acrosomal sperm proteins was inoculated into female monkeys to test whether specific antibodies to each component immunogen could be elicited in sera and whether antibodies elicited by the vaccine affected in vitro fertilization. Acrosomal proteins, ESP, SLLP-1, SAMP 32, SP-10 and SAMP 14, were expressed with his-tags, purified by nickel affinity chromatography and adsorbed to aluminum hydroxide. Five female cynomolgus monkeys were inoculated intramuscularly three times at monthly intervals. All five monkeys developed both IgG and IgA serum responses to each recombinant immunogen on Western blots. Each serum stained the acrosome of human sperm and bound to the cognate native protein on Western blots of human sperm extracts. By ELISA, all monkeys developed IgG to each immunogen, with the highest average absorbance values to ESP, SAMP 32 and SP-10, followed by lower values for SLLP-1 and SAMP 14. IgA was also generated to each component immunogen with the highest average absorbance values to SLLP-1 and SP-10. For antigens that induced an IgA response, the duration of the IgA response was longer than the IgG response to the same antigens. This study supports the concept that a multivalent contraceptive vaccine may be administered to female primates evoking both peripheral (IgG) and mucosal (IgA) responses to each component immunogen following an intramuscular route of inoculation with a mild adjuvant, aluminum hydroxide, approved for human use.     

Transmission of immunoglobulin to foetal and neonatal mice

Transmission of immunoglobulin (Ig) classes and subclasses from mother to foetus and to neonate, and the survival of maternal Ig in the circulation of the young mouse up to 40 days after birth, has been quantitated in Balb/c homozygous and (Balb/c×SJL/J)F₁ matings using isotype-specific heteroantisera in radial immunodiffusion in gel assays. The transfer of anti-allotype (anti-Ig-1^b(γ2a)) antibodies from immunised Balb/c mothers (Ig-1¹) to F₁ heterozygote (Ig-1^ab) offspring was measured by passive haemagglutination of Ig-1^b target allotype-coated sheep red blood cells. A small but significant level of transmission of Ig to the foetus occurs by the 15th day of gestation (5 days before birth) but the bulk of passively acquired Ig is derived from the milk after birth. All Ig acquired in utero and later across the intestinal barrier is exclusively of IgG isotypes (γ1, γ2a, γ2b) even though the milk has a large predominance of IgA. An appreciable level of maternally derived antibody is maintained in the circulation of the young mouse 24 days or more after gut ‘closure’ on the 16th day post-partum.     

Impact of delivery type on EGF and IGF-1 concentration in umbilical blood of newborns and their mothers' milk

Peptide growth factors, including EGF and IGF-1, play a substantial role in child's growth and maturation processes. Growth factors found in mother's milk can modify development of the newborn and the infant, especially in the area of alimentary tract differentiation and maturation. OBJECTIVES: Study was undertaken to evaluate impact of the delivery type on EGF and IGF-1 concentration in the umbilical blood of newborns and their mothers' milk. MATERIAL AND METHODS: Sixty eight newborns and their mothers were examined. EGF and IGF-1 concentration was measured in serum of venous umbilical blood as well as in the mothers' milk collected on the first day of lactation. To measure EGF and IGF-1 concentration radioimmunoassay method (RIA) was applied. RESULTS: No correlation was found between the concentration of the two growth factors in umbilical blood and the delivery type. Neither significant difference was found between EGF concentration in the milk of the mothers who had spontaneous labour and the factor concentration in the milk of the mothers who had a caesarean section. Contrary to EGF, IGF-1 concentration in the milk of the mothers who had a caesarean section was lower than in the milk of the mothers who had a spontaneous delivery. However, significant differences were observed only in a group of mothers of newborns born at term. CONCLUSIONS: Caesarean section may disturb mechanisms of IGF-1 synthesis and release to mother's milk in the initial stage of lactation.     

Blood-stained maternal milk: prevalence, characteristics and counselling

Blood-stained maternal milk at delivery and during lactation was prospectively studied in 7774 livebirths over a period of 2 years (1986-1988). Eight mothers had this atypical breast discharge, a prevalence rate of 1:971 livebirths (0.1%). The characteristics of this phenomenon were: early appearance (frequently a short time after delivery), with normal bacteriologic and cytologic investigations, disappearance in 2 to 5 days, without adverse effects on the mothers and their babies, no recurrence after cessation, and occurrence in the previous pregnancies (3 of the 5 multipara). As a result, the best policy is to reassure the parents about the benign and transient course of this condition and to recommend continuation of breast feeding.     

用ELISA法对不明原因不育夫妇血清和生殖道分泌液中抗精子抗体的研究

本文采用ELISA间接法对30对不明原因的不育夫妇血清及生殖道分泌液中ASA的阳性率、种类(IgG、IgM、IgA)及分布情况进行了研究。男性病人组血清中ASA阳性率为13.3%,精浆中为16.7%,和对照组相比无统计学意义。女性病人组血清中ASA阳性率为23.3%,宫颈粘液中为33.3%,和对照组相比均有显著差异。在不明原因的不育夫妇中,ASA主要发生在女方。检测结果表明,血清、精浆和宫颈粘液中均存在有IgG、IgM、IgA类ASA。但血清中主要为IgG、IgM类ASA,精浆及宫颈粘液中主要为IgA、IgG类ASA。ASA可同时存在于血清或生殖道分泌液中,也可单独存在于血清或生殖道分泌液中。     

Chlamydia trachomatis in term pregnancy. isolation and serological study with a case report

The prevalence of cervical Chlamydia trachomatis infection in healthy, symptomless full-term pregnant women (n = 92) was found to be low (1.1%). Chlamydial cervical IgA antibodies, as measured by solid-phase radioimmunoassay (RIA), were found in 5.3%, but amniotic fluid chlamydial RIA IgA antibodies were almost absent. Serum IgG antibodies were measured with indirect immunofluorescence (IF). Of the mothers 9.8% had a titer greater than or equal to 1:64, correlating closely with the figure of 10.9% for infants' cord-blood IF serology. Finally, a case report is presented. A child born to a Chlamydia trachomatis positive mother developed isolation positive chlamydial pneumonia.     

The Influence of Breast Surgery,Breast Appearance,and Pregnancy-Induced Breast Changes on lactation Sufficiency as Measured by Infant Weight Gain

ABSTRACT: We conducted a prospective study of the associations between several biologic and surgical breast factors and the onset of lactation in 319 healthy, motivated, primiparous women who were breastfeeding term, healthy, appropriate for gestational age or large for gestational age infants. During the last trimester of pregnancy, subjects' breasts were examined for surgical incisions, size, symmetry, and nipple protuberance, and women estimated their prenatal breast enlargement. At two visits in the first two weeks postpartum, infants were weighed naked, and mothers reported the magnitude of postpartum breast engorgement when their milk came in. Breastfeeding was evaluated at each visit, and interventions were recommended for problems, with emphasis on maximizing milk yield. Lactation was deemed sufficient when an exclusively breastfed infant achieved an average weight gain of 28.5 g or more per day between the two visits. Infants gaining less than 28.5 g per day with breast milk exclusively, and those requiring formula supplement returned for a third visit at or before 21 days of age, when final lactation outcome was assessed based on weight gain between the second and third visits. Within three weeks postpartum 85 percent of the mothers achieved sufficient lactation, whereas 15 percent had persistent milk insufficiency despite intensive intervention. Of the study population, 6.9 percent had undergone previous breast surgery. Women with periareolar breast incisions were nearly 5 times more likely to have lactation insufficiency than were those without surgery (relative risk [RR] = 4.55; 95 percent confidence interval [CI] = 2.21–9.43; P < 0.001). Insufficient lactation was significantly associated with minimal prenatal breast enlargement (P < 0.02) and minimal postpartum breast engorgement when milk came in (P < 0.001). Although not statistically significant, women with inverted nipples were more likely to have lactation insufficiency compared with those with normal nipples (RR = 2.94; 95% CI 1.05–8.20; P= .07). The findings from this study indicate that certain biologic and surgical breast variables are associated with lactation insufficiency.     

Endometrial autoantigens eliciting immunoglobulin (Ig)G, IgA, and IgM responses in endometriosis

Endometrial antigens from patients with endometriosis and fertile controls were tested against immunoglobulin (Ig)G, IgA, or IgM in endometrium, serum, and peritoneal fluid (PF) of the patients and controls by Western blot analysis. Endogenous IgG was detected in 78% of the endometria or endometriosis implants from the patients and 22% of the endometria from the controls. Endometrial IgA and IgM were detected in few controls and patients. Immunoglobulin G in the serum and/or PF of patients with endometriosis was specifically directed against antigens with molecular weights of 34, 42, 82, 94, 110, 120, and 140 kd found in the patients' endometrium or endometriosis implants. Immunoglobulin A and IgM in the serum or PF of the patients and controls were nonspecific in their reactivity. Endometrial antigens found in endometrium or implants of patients with endometriosis, and eliciting IgG responses, may be relevant to autoimmunity in endometriosis.     

Mood states and milk output in lactating mothers of preterm and term infants.

The purpose of this study is to compare psychological distress via both negative and positive mood states between 2 different groups of lactating mothers during the first 6 weeks postpartum with a large sample. Mood states were measured using the Multiple Affect Adjective Check List-Revised by a convenience sample of newly delivered mothers from 4 tertiary care units in Illinois. Preterm mothers' negative mood states of anxiety, depression, hostility, and dysphoria were significantly greater than those reported for term mothers. For the positive mood states of positive affect and PASS (positive affect + sensation seeking), preterm mothers had significantly lower scores than term mothers; there were no differences for the positive mood state, Sensation Seeking. Maternal perceived mood states had no apparent effect upon lactation as measured by milk volume produced. Further study is warranted to determine what factors influence milk output in mothers of preterm and term infants who are at risk for lactation failure.