Placental Transfer Of Antibodies Research Articles

Placental transfer of measles antibodies: effect of gestational age and maternal vaccination status

Despite nationwide measles vaccination coverage in Israel of over 90%, repeated outbreaks of measles have spread from isolated communities with poor immunization uptake. Some severely affected individuals were children under 1 year of age, including premature infants. We evaluated the serological status of 195 newborn infants and their 161 mothers divided into four groups: vaccinated mothers (VMs) and premature infants, VM and full term infants, naturally immunized mothers (NIMs) and premature infants, NIM and full term infants. Maternal and cord blood measles antibody titers were determined by haemagglutination inhibition (HI) test and microneutralization test (mNT). Fewer than 40% of preterm infants of VM and less then 70% of preterm infants of NIM had protective titers at birth. The results of this study may aid in formulating new measles vaccination recommendations for preterm infants.

Placental and breast transfer of antibodies after maternal immunization with polysaccharide meningococcal vaccine: a randomized, controlled evaluation

We evaluated the strategy of maternal immunization with Neisseria meningitidis (Nm) vaccine in Asian mothers, to assess potential protection of infants, including by breast milk. One hundred and fifty-seven women in the third trimester were randomized to receive a single dose of the polysaccharide Nm ( n=75) or a control vaccine ( n=82). Group A Nm IgG levels were measured in maternal and infant sera, and specific IgA in breast milk. A 5.6-fold rise of Nm IgG antibody was observed among the Nm vaccinees. At delivery, geometric mean titres (GMTs) of Nm IgG antibody in Nm mothers was 12.5 μg/ml versus 4.97 μg/ml, with a mean infant/maternal antibody ratio of 0.56. Infants of Nm vaccinees had mean IgG levels of 6.9, 2.3, 1.2 and 0.6 μg/ml at 0, 6, 14 and 22 weeks, significantly higher than in control children up to 14 weeks. Anti-Nm IgA levels in milk were 6.8 to 2.0 μg/ml, significantly higher in Nm vaccinees till 6 months. Immunization during pregnancy is safe for both mothers and infants, and provides infants with significantly increased levels of specific IgG for 2–3 months and oral IgA for 6 months.

Neonatal Liver Disease Associated with Placental Transfer of Anti-mitochondrial Antibodies

Background: Anti-mitochondrial antibody is the diagnostic hallmark of primary biliary cirrhosis. Its role in the aetiology of primary biliary cirrhosis is controversial. Methods: Two cases of neonatal hepatitis seropositive for anti-mitochondrial antibody are described. Anti-mitochondrial antibody Ig isotype and epitopic specificity were investigated by immunofluorescence and enzyme immunoassays. Results: In both infants anti-mitochondrial antibody was of the G class, mainly G1 and G3 subclasses, and reacted with two synthetic peptides reproducing major M2 epitopic regions: inner lipoyl domain pyruvate dehydrogenase complex (PDC)-E2162-176 and PDC-E3 binding protein (PDC-E3BP)86-100. One infant also reacted with outer lipoyl domain PDC-E235-49, and 2-oxoglutarate dehydrogenase complex (OGDC)-E299-113. An identical pattern of reactivity was present in their mothers, indicating the maternal origin of the antibodies. Anti-mitochondrial antibody disappeared in the infants with the disappearance of the liver pathology. Conclusions: The simultaneous disappearance of hepatitis and anti-mitochondrial antibody in the infants suggests a possible causal link between the two.

Materno-foetal transfer of H. influenzae and pneumococcal antibodies is influenced by prematurity and low birth weight: implications for conjugate vaccine trials

The influence of prematurity and low birth weight (LBW) on transplacental transfer of Haemophilus influenza type B and Streptococcus pneumoniae antibodies was assessed in 213 mothers and their neonates from Gambia. Paired maternal and cord serum samples were tested for specific IgG antibody titres for H. influenza and S. pneumococcus antigens using enzyme linked immunosorbent assay. Prematurity and LBW was significantly associated with reduced placental antibody transfer for these antigens. The reduced materno-foetal transfer of these antibodies in this vulnerable population of babies may further predispose them to more bacterial infections. These findings are of practical importance to the vaccination strategies.

The influence of prematurity and low birthweight on transplacental antibody transfer in a rural West African population.

To determine the influence of prematurity and low birthweight (LBW) on transplacental antibody transfer. In a physician-blinded, cross-sectional study of 213 mother--baby pairs in the labour ward of Bansang Hospital, The Gambia, paired maternal and cord serum samples were tested for specific IgG antibody titres for measles virus (MeV), herpes simplex virus type 1 (HSV1), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid (TT) and diphtheria toxoid (DT) antigens using enzyme linked immunosorbent assay (ELISA). Prematurity was significantly associated with reduced placental antibody transfer for MeV, HSV1, TT, DT, RSV and VZV. Maternal antibody transfer for MeV, HSV1, TT, DT, RSV and VZV was significantly lower in neonates with LBW than in babies with adequate birthweight (ABW). Materno--foetal transfer of antibodies is impaired in prematurity and LBW babies in this Gambian population. Reduction in antibody transfer may further predispose these already vulnerable neonates to bacteria and viral infections. Therefore, alternative vaccination strategies, including earlier vaccination schedules, are needed to provide better protection to these young infants.

Factors determining prevalence of maternal antibody to measles virus throughout infancy: a review.

The effectiveness of vaccination against measles, the leading cause of vaccine-preventable deaths in infants globally, is greatly impacted by the level of maternal antibody to measles virus (or "measles maternal antibody"; MMA) during infancy. Variation in the prevalence of maternal antibody to measles virus between infant populations across countries and sociodemographic strata is poorly understood. We reviewed the literature on the prevalence of MMA, focusing on 3 principal determinants: starting level of maternal antibody, placental transfer of maternal antibody, and rate of decay of maternal antibody after birth. Our review identified placental transfer as an important determinant, with greater efficiency found in studies performed in developed countries. Placental transfer was influenced by gestational age, human immunodeficiency virus infection, and malaria. Antibody levels in mothers varied widely between countries, although predictably according to vaccination status within populations. Rates of antibody decay across studies were similar. Future studies should evaluate the utility of the cord blood level of MMA as a predictor of vaccine efficacy in infancy; inclusion of World Health Organization international reference sera will facilitate comparisons. Greater understanding of the determinants of the prevalence of MMA will help national policy makers determine the appropriate age for measles vaccination.

Placental transfer and decay of varicella-zoster virus antibodies in preterm infants

Objectives: To compare the placental transfer of maternal varicella-zoster (VZV) antibodies to preterm and term infants and to investigate antibody decay during the first 6 months of life in the preterm infants. Study design: Maternal and umbilical cord blood samples were taken from 113 healthy mother-newborn pairs: 64 term (gestational age ≥37 weeks) and 49 preterm (gestational age ≤35 weeks). Premature infants were further tested at 1, 2, and 6 months. Anti-VZV antibody to membrane antigen was measured with the immunofluorescent technique. Results: Preterm infants of gestational age ≤28 weeks had positive cord antibody and a geometric mean titer significantly lower than those in preterm infants of gestational age 29 to 35 weeks and term infants (25% vs 95% and 95%, respectively, P <.001 for each, and 2.5 ± 2.2 vs 10.5 ± 2.4 and 12.6 ± 2.4, respectively, P <.001 for each). There was no difference between the preterm 29 to 35 weeks of gestation and term groups. Fetal-maternal ratios for both preterm groups were <1 and were significantly less than the fetal-maternal ratio in the term infants. The transfer of maternal antibodies to term infants was significantly greater than to the 29- to 35-week preterm infants (P =.01). At 2 months of age, 25% of 29- to 35-week preterm infants and no preterm infant ≤28 weeks had a positive titer. At 6 months of age, all preterm infants were seronegative, and the geometric mean titer in both groups declined to undetectable levels. Conclusion: Transplacental transfer of maternal VZV antibodies is diminished in preterm infants. VZV antibody levels are significantly lower in preterm infants born at ≤28 weeks’ gestational age compared with those in preterm infants 29 to 35 weeks’ gestational age and term infants. Anti-VZV titers decrease to undetectable levels in preterm infants by 6 months of age or earlier; thus these infants appear to be susceptible to chickenpox before the scheduled 12-month vaccination. (J Pediatr 2000;137:85-9)

Social stress in pregnant squirrel monkeys (Saimiri boliviensis peruviensis) differentially affects placental transfer of maternal antibody to male and female infants.

The capacity of prenatal stress to disrupt the placental transfer of maternal antibody was evaluated in neonatal squirrel monkeys (Saimiri boliviensis peruviensis) gestated under different pregnancy conditions. Normal squirrel monkey offspring (n = 63) were compared with infants generated from pregnancies that involved either a single or 3 periods of disturbance (ns = 21 and 29, respectively). At parturition, levels of antibody (IgG) were determined in mothers and neonates. Only the chronic disturbance condition significantly altered antibody levels in the mothers, resulting in lower IgG. Antibody transfer to the fetus was also affected only by chronic disturbance. In this case the effect was bidirectional, influenced by the sex of the infant. Males were born with lower levels, whereas female infants actually had higher-than-normal IgG, despite lower titers in their mothers. Because virtually all IgG is derived from the prenatal transfer of maternal antibody, it indicates that the sex of the fetus differentially affected this placental process. The IgG receptor may have been up-regulated selectively on the placentas of female fetuses, compensating for reduced antibody in the disturbed mothers.

Teratogen update: maternal myasthenia gravis as a cause of congenital arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is defined as nonprogressive congenital contractures that generally result from lack of fetal movement in utero. AMC is a feature of many congenital disorders caused by genetic, environmental, or other factors. One rare cause of AMC is maternal myasthenia gravis (MG). This is an autoimmune disorder, caused by antibodies to the nicotinic acetylcholine receptor (AChR), and resulting in weakness of voluntary muscles. In 10-15% of babies born to MG mothers, transient signs of MG are noted after placental transfer of anti-AChR antibodies. In a few cases, AMC predominates. We review the role of antibodies to AChR in MG and in AMC associated with maternal antibodies to AChR. In anti-AChR antibody-associated AMC, fetal or neonatal death is common; other deformities or CNS abnormalities are common as well. The condition usually recurs in each pregnancy unless the mother is treated for MG, but some mothers are asymptomatic. The maternal antibodies cross the placenta and block the function of the fetal isoform of the AChR leading to fetal paralysis. Injection of maternal plasma into pregnant mice results in AMC in mouse fetuses. Some women with recurrent AMC in their babies have no detectable anti-AChR suggesting the presence of antibodies to other fetal muscle or neuronal proteins. Although rare, anti-AChR-associated AMC is potentially treatable and can be diagnosed by a routine antibody test. The mouse model can be used to investigate the role of these and other maternal antibodies in causing congenital conditions.

Placental transfer of IgG antibodies against Haemophilus influenzae type b capsular polysaccharide in Brazilian term and preterm newborns.

Placental transfer of antibodies to polysaccharide antigens is still a controversial subject. The incidence of invasive Haemophilus influenzae type b (Hib) infections is high in countries where the vaccine has not been included in routine immunization schedules. In the present work, we proposed to evaluate the natural immune response to Hib capsular polysaccharide in term and preterm Brazilian newborns and their respective mothers. Although the means, medians, and ranges of antibody titres in paired maternal and cord sera from preterm neonates were similar, the maternal levels were slightly higher than the cord levels and a poor correlation between these levels was verified. Term neonates showed similar antibody levels to those of their respective mothers and a very significant correlation between these levels was observed.

Placental transfer of maternal rubella antibodies to full-term and preterm infants.

Premature infants are vulnerable to infections, partly because of the low transplacental transfer of maternal antibodies. The present study investigated the placental transfer of maternal rubella-specific antibodies to full-term and preterm infants. The study group consisted of 133 healthy, native Israeli mothers and their 159 newborns. Of these, 69 were full-term infants (gestational age > 37 weeks) of 69 mothers, and 90 were preterm infants (gestational age < 35 weeks) of 64 mothers. Antibody titers against rubella were measured in maternal and umbilical cord blood samples by hemagglutination inhibition and microneutralization techniques. There was no significant difference in the level of protection and in geometrical mean titers by hemagglutination between the full-term and preterm groups. Conversely, significant differences in geometric mean titers of neutralizing antibodies were found between full-term and preterm infants, e.g., 65.9 and 39.8, respectively (P < 0.001). Very low birth weight preterm infants are at greater risk of rubella infection during the first year of life, due to the diminished transfer of neutralizing maternal antibodies. Therefore, earlier vaccination of this group may be beneficial.

The influence of prematurity and low birthweight on transplacental antibody transfer in Sri Lanka.

The influence of gestational age, the neonate's birthweight, and maternal age, weight, height and parity on transplacental antibody transfer was assessed in 141 mothers from Sri Lanka and their neonates. Paired blood samples were collected from the mothers and the umbilical cords of the newborns. The sera separated from these samples were categorized as: preterm but adequate birthweight (< 37 weeks' gestation and birthweight > or = 2500 g); term but low birthweight (> or = 37 weeks' gestation and birthweight < 2500 g); or term and adequate birthweight (> or = 37 weeks' gestation and birthweight > or = 2500 g). Neonatal and maternal sera were assessed, in ELISA, for specific IgG antibodies against measles virus (MeV), herpes simplex virus type-1 (HSV1), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid (TT), diphtheria toxoid (DT), and Streptococcus pneumoniae (Pn) and Haemophilus influenzae type-b (Hib) capsular antigens. Placental antibody transfer to certain antibody specificities was significantly lower in preterm neonates than term neonates. Thus the ratios between geometric mean cord antibody levels and geometric mean maternal antibody levels (the antibody-transfer ratios) were lower in preterm sera than term sera, for MeV (1.51 v. 2.03; P = 0.03), HSV1 (1.29 v. 1.76; P = 0.04), VZV (0.96 v. 2.50; P = 0.01), TT (1.13 v. 1.33; P = 0.04), DT (1.03 v. 2.39; P = 0.02), Pn (0.68 v. 0.98; P = 0.01) and Hib (0.58 v. 0.98; P = 0.00). Geometric mean levels of antibody to MeV, VZV, TT, DT and Pn were also significantly lower in preterm neonates than term. Compared with the values for 'adequate-birthweight' sera, low birthweight was independently associated with significantly lower levels of antibody transfer, for MeV (with antibody-transfer ratios of 1.51 v. 2.03; P = 0.02), VZV (0.99 v. 2.50; P = 0.03), TT (1.01 v. 1.33; P = 0.04) and DT (1.16 v. 2.39; P = 0.04) and significantly lower levels of antibodies to MeV, HSV1, VZV, TT, DT and Pn in the neonates. Maternal age, weight, height and parity had no independent influence on placental IgG transfer for antibodies to any of the pathogens investigated. These results demonstrate that prematurity and low birthweight may influence the level of maternally acquired immunity in Sri Lankan neonates.

Human serum β2-microglobulin levels: correlation with total serum IgG and placental IgG transfer in HIV-infected and non-HIV infected individuals

The acquisition of maternal immunoglobulin G (IgG) is fundamental to the immune defence of the neonate. The receptor responsible for IgG transfer across the human placenta has also been implicated in the maintenance of IgG levels in the circulation. β 2-microglobulin is part of the Fc receptor (FcR) that has recently been purified from the human placenta. In HIV infection, increasing serum levels of total IgG and β 2-microglobulin are observed as the disease progresses. Herein, we have investigated the correlation between β 2-microglobulin and total serum IgG levels in HIV-seropositive mothers and their term neonates (HIV group, n=37), as well as in HIV-seronegative mothers and their term neonates (control group, n=50). Serum maternal β 2-microglobulin was directly correlated with total serum IgG levels in HIV-infected mothers ( r=0.58; P=0.0002), but not in healthy HIV-seronegative mothers ( r=−0.20; P=0.16). Maternal serum β 2-microglobulin was also inversely correlated with placental antibody transfer of total IgG in mother-newborn pairs from the HIV group ( r=0.38; P=0.02), but not from the control group ( r=0.15, P=0.31). These results seem to indicate that, in HIV infection, elevated serum β 2-microglobulin levels could be involved in maintenance of abnormally high total serum IgG concentrations; by interfering with the binding of IgG to Fc receptors at the maternal-fetal interface, they might also reduce IgG transfer. By contrast, in normal non-HIV infected individuals, serum β 2-microglobulin levels do not appear implicated in regulation of these two phenomena.

Placental antibody transfer: influence of maternal HIV infection and placental malaria

AIMTo determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer.METHODSOne hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord...

Placental transfer of IgG and IgG subclass antibodies anti-purified Escherichia coli LPS O16, O6 and O111.

We evaluated 22 paired maternal and cord sera regarding the presence of IgG and IgG subclasses against purified Escherichia coli LPS O6, O16 and O111 employing ELISA for titre and avidity analysis, isoelectric focusing associated with affinity-blotting for spectrotypic analysis, and the Western-blotting technique for recognition of the various bands in lipopolysaccharide (LPS). Levels of anti-LPS IgG antibodies in cord sera were equivalent to their respective maternal sera, showing a significant correlation (P < 0.0001). IgG1 antibody levels were higher in cord sera than in maternal sera (P < 0.005 for anti-O111, P < 0.05 for anti-O16 and P < 0.02 for anti-O6). Cord IgG2 antibody levels were not different from the maternal levels (P > 0.1). The levels of IgG3 and IgG4 were undetectable. The avidity of anti-O6 and anti-O111 IgG in 10 cord sera showed an extremely significant correlation with maternal antibody avidity (P < 0.0001). Identical patterns of recognition were found in the paired samples analysed by Western blotting. Most of the serum samples recognized the O-repetitive chains and also the region corresponding to core and lipid A. Although the antibody spectrotypes varied among individuals, paired cord and maternal serum samples showed identical patterns. Our findings suggest the occurrence of placental transfer of IgG antibodies against LPS O6, O16 and O111, mainly involving the IgG1 or IgG2 subclasses.

Placental Transfer of Maternal Measles Antibodies to Pre-Term and Full-Term Infants 839

Objective: To investigate and compare placental transfer of maternal Rubeola antibodies to pre-term and full-term infants.

Placental Transfer of Maternal Rubella Antibodies to Full-term and Pre-term Infants 873

Placental Transfer of Maternal Rubella Antibodies to Full-term and Pre-term Infants 873

Placental transfer favours high avidity IgG antibodies

The aim of the present study was to evaluate if maternal‐foetal antibody placental transfer may be affected by antibody avidity. We compared the avidity index (AI) of IgG antibodies to tetanus toxoid (TT) and to type 3 pneumococcal antigen (Pn) in cord blood of 10 healthy term and 8 preterm infants and in their mothers' sera at delivery. In order to evaluate whether a heavier antigenic exposure may influence the placental transfer, we also studied 15 Pakistani maternal sera and cord blood pairs. TT‐ and Pn‐specific antibody AI was significantly higher in Italian and Pakistani term infants than in their mothers, while a significant difference in specific TT antibody AI, but not in specific Pn antibody AI was observed between preterm infants and their mothers. Italian and Pakistani cord blood/maternal serum pairs showed comparable values of AI. Our data suggest that high avidity antibodies preferentially cross the placenta; this seems to start early during gestation and appears to be related to the nature of the antigen to which the antibodies are directed, but not to the degree of antigenic exposure.

Placental transfer of maternal poliovirus antibodies in full-term and pre-term infants

This study was designed to investigate the placental transfer of maternal poliovirus antibodies in full-term and pre-term infants. Two hundred healthy, Israeli born mothers and their infants, were enrolled immediately after birth. The study population comprised two groups: a full-term group of 150 mothers and their infants, and a pre-term group of 50 mothers and their infants (gestational age <35 weeks). Maternal and umbilical cord blood samples were taken in all cases. Antibody titers against the three poliovirus serotypes and a polio virus type 1 strain that caused an outbreak in 1988 (epidemic strain 1) were measured by a microneutralization system. The proportion of individuals with protective titers against each of the poliovirus types tested was slightly lower in the infants compared with their mothers. When protection to all strains combined was tested, the difference between mothers and infants was significant ( P < 0.05). Transplacental transfer to epidemic strain 1 was less effective—12% of the premature infants were not protected against it at birth. The geometric mean titers against poliovirus types 1, 3 and epidemic type 1 strain were significantly lower in the pre-term group than in the full-term group. In both the full-term and pre-term groups there were significant linear correlations between the maternal and neonatal antibody titers for each of the polio viruses tested. For all poliovirus types, the transfer of maternal antibodies to the full-term infant was significantly higher than the transfer of maternal antibodies to the pre-term infant ( P < 0.001). Owing to diminished transfer of maternal antibodies, pre-term infants are at greater risk of poliovirus infection.

Placental transfer favours high avidity IgG antibodies.

The aim of the present study was to evaluate if maternal-foetal antibody placental transfer may be affected by antibody avidity. We compared the avidity index (AI) of IgG antibodies to tetanus toxoid (TT) and to type 3 pneumococcal antigen (Pn) in cord blood of 10 healthy term and 8 preterm infants and in their mothers' sera at delivery. In order to evaluate whether a heavier antigenic exposure may influence the placental transfer, we also studied 15 Pakistani maternal sera and cord blood pairs. TT- and Pn-specific antibody AI was significantly higher in Italian and Pakistani term infants than in their mothers, while a significant difference in specific TT antibody AI, but not in specific Pn antibody AI was observed between preterm infants and their mothers. Italian and Pakistani cord blood/maternal serum pairs showed comparable values of AI. Our data suggest that high avidity antibodies preferentially cross the placenta; this seems to start early during gestation and appears to be related to the nature of the antigen to which the antibodies are directed, but not to the degree of antigenic exposure.