Placental transfer and decay of maternally acquired antimeasles antibodies in Nigerian children

BACKGROUND: In developing countries vaccination against measles virus (MV) is generally administered at 9 months of age, although it is well-documented that protection of most infants by passively acquired maternal MV antibodies is waning before immunization is given. The purpose of this study was to investigate the decay of maternally derived MV antibodies in Nigerian infants as well as to compare a German and Nigerian cohort of paired mothers and newborns regarding the placental transfer efficiency of MV-specific IgG and total IgG antibodies. METHODS: MV-specific IgG antibodies were measured with a commercially available MV-enzyme-linked immunosorbent assay, a recombinant hemagglutinin enzyme-linked immunosorbent assay as well as a neutralization assay. Total IgG values were determined with a standard immunoturbidimetric test. RESULTS: Anti-MV IgG titers were twice as high in German newborns as in Nigerian newborns. An increased concentration of immunoglobulins transferred via the placenta was found only in the German cohort. High concentrations of total maternal IgG reduced the concentration of MV-specific as well as total IgG that crossed the placenta. Furthermore only 17% of the 4-month-old Nigerian infants were still protected against measles. Antibodies had a biologic half-life of 33 days and a biochemical half-life of 48 days. CONCLUSIONS: Our findings demonstrate that the decay of passively acquired MV antibodies occurred even more rapidly than expected resulting in susceptibility to MV in most of the 4-month-old infants in Nigeria. Furthermore transfer of maternal anti-MV IgG and total IgG antibodies to the newborn was more efficient in the German cohort compared with the Nigerian group. These findings suggest the use of alternative vaccination strategies in developing countries to possibly reduce the window of susceptibility against measles.     

Placental transfer of tetanus antibodies and protection of newborn infants

Total IgG and tetanus antibodies were evaluated in 2 series of mother-child pairs: 50 in Paris and 134 in Africa. All pregnancies had been normal and birth weights greater than 3 kg. Cord blood mothers tetanus antibodies ratios were 1.5 in Paris and 0.98 in Libreville (p less than 0.01) respectively. Some African children were not protected, either due to the lack of response of their mothers to immunization (2.2%) or to an insufficient antibodies transplacental transport (2.9%), or to the lack of immunization of mothers (5.9%). On the contrary, all European children were protected, in spite of low maternal antibody levels. Likewise, in Paris cord blood IgG level was 12.24 g/l vs 9.42 in mothers (cord blood/mother ratio: 1.34) and in Africa 18.4 g/l in cord blood and 22.3 g/l in mothers (cord blood/mother ratio: 0.88; p less than 0.01). The correlations between maternal IgG levels and placental transfer rates indicate that the transplacental active transfer is limited by common high IgG levels in Africa, thus contributing to a decrease in protection of neonates, especially against tetanus in which humoral responses predominate.     

Immunoglobulin subclass antibodies to varicella-zoster virus

Commercially available mouse monoclonal antibodies to human IgG subclass (IgG1 to IgG4) were applied to an enzyme-linked immunosorbent assay to measure IgG subclass-specific antibodies to varicella-zoster virus in children naturally infected with varicella-zoster virus and in varicella vaccine recipients. In children naturally infected with varicella-zoster virus, IgG 1 antibody was detected 2 weeks after onset of the disease in all cases, its activity increased at 1 month after onset, and almost equal antibody value was maintained 10 years after infection. This pattern of antibody response was similar to that of total IgG antibody to varicella-zoster virus after natural infection. On the other hand, low antibody activity was found in IgG2 only at 1 month of the disease. The highest antibody level of IgG3 was shown 2 weeks after onset of the disease; then, it gradually decreased, and no antibody activity was detected 10 years later. IgG4 antibody was first detected 1 month after onset and an almost equal level of antibody was shown 10 years after the disease. After inoculation of children with a live varicella vaccine, in contrast, IgG subclass antibody responses to vaccine recipients were almost equal to those after natural 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.     

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.     

Transplacentally acquired immunoglobulin G antibodies against measles, mumps, rubella and varicella-zoster virus in preterm and full term newborns

IgG antibody values against measles, mumps, rubella and varicella-zoster virus in 71 full term and 101 preterm infants and their 152 mothers and the decay of maternally acquired antibodies during infancy were studied. Both magnitude of transplacental antibody passage and cord blood antibody values correlated with gestational age. After 6 months preterm infants born before 32 weeks of gestation had lost maternal antibodies.     

Placental transfer of tetanus antibodies and protection of the newborn

The aim of the study was to compare the placental transfer of tetanus toxoid antibodies (TTAB) and total IgG in Africa, where we had previously demonstrated a lack of transmission from mother to the newborn of measles antibodies. Two series of mother-child pairs, 45 in Paris and 134 in Libreville, Gabon, Central Africa, were measured after full-term pregnancies and normal deliveries. Means of ratios of cord/mother concentrations for TT AB and IgG were, respectively, 2.52 and 1.28 in Paris and 0.98 and 0.82 in Gabon. In 11 pairs from Libreville no TT AB were found in mother and cord blood, but in four other African newborns (3 per cent), the mother transmitted TT AB which were lower than protective level against tetanus. Other data (negative correlation between mother IgG and cord/mother ratio of corresponding TT AB concentrations, and better transmission of TT AB in the low range of maternal IgG) indicate that the limitation of active placental transfer of antibodies is related to the high maternal IgG level common in Africa.     

Cardiovascular fluctuations and transfer function analysis in stable preterm infants

To examine the baroreceptor reflex function, a beat-to-beat analysis between systolic blood pressure (SBP) and R-R interval fluctuations was studied in 10 stable appropriate-for-gestational age preterm infants (range, 27.2-33.7 wk) in the first postnatal week during quiet sleep. Spectral power analysis, using fast Fourier transform, and transfer functions (gain and phase difference) between SBP and R-R fluctuations were estimated in a low-frequency band (LF, 0.03-0.2 Hz) and high-frequency band (HF defined as the frequency band between the 10th and 90th centiles of the individual respiratory frequency). The LF/HF ratio reflects the sympathovagal balance. The mean frequency (+/-SD) of LF peaks was centered at 0.07 +/- 0.02 Hz. The mean frequency (+/-SD) of the individual HF band was 0.82 +/- 0.21 Hz. The LF/HF ratio in the R-R interval series [median, 29; interquartile range (IQR), 16-40] was higher than in the SBP series (median, 8; IQR, 4-14). The gain between R-R interval and SBP fluctuations (median, 4.2 ms/mm Hg; IQR, 2.4-5.0) in the LF band was higher than in the HF band (median, 1.7 ms/mm Hg; IQR, 1.4-3.0). SBP fluctuations lead R-R interval fluctuations in the LF band with a median phase difference of +96 degrees (IQR, 67-132). At LF the fluctuations in SBP precede changes in R-R interval with a time delay of 3.8 s. These observations indicate a dominant role of the sympathetic system in stable preterm infants in comparison with published adult values. Cross-spectral analysis allows a test for tracking the development of the sympathetic system in neonates.     

Antimeasles antibodies in preterm infants during early infancy in Turkey

AIM: To measure maternally derived measles antibodies in sera of premature infants at birth and seropositivity rates in early infancy in a rural area of central Turkey. METHODS: 65 premature and 24 full-term infants born in Erciyes University Hospital and their mothers were recruited to a longitudinal, prospective study. The infants were divided into three groups by gestational age: group A, <33 weeks; group B, 33-37 weeks; group C, >37 weeks. For specific analyses, the groups were subdivided into groups Al, B1 and C1 (infants of naturally immunised mothers) and A2, B2 and C2 (infants of vaccinated mothers). Blood samples were obtained from mothers and infants after delivery. The infants were re-evaluated at 2, 4 and 6 months of age. RESULTS: Of 25 mothers, 20.3% were seronegative for measles antibodies. Twenty of the mothers had not been vaccinated. The percentages of seronegative infants at birth were 24.2% (n=8), 12.5% (n=4) and 0% (n=0) in groups A, B and C, respectively. No infants were seronegative at birth in Al, B1 or C1. Mean levels of antimeasles antibodies in all naturally immunised mothers were significantly higher than in vaccinated mothers. Antibody levels in all infants decreased rapidly with increasing age. Gestational age at birth [beta=0.179, t=3.359, 95% confidence interval (CI) 0.0001-0.0001, p<0.05], birthweight (beta=0.637, t=9.691, 95% CI 0.057-0.086, p<0.05) and maternal naturally immunised status (beta=0.168, t=2.825, 95% CI 0.002-0.014, p<0.05) were significantly associated with antibody levels after birth. In all groups of naturally immunised mothers, the percentages of seronegative infants were significantly lower than in vaccinated mothers at birth and at 2, 4 and 6 months of age. CONCLUSION: The current recommendation to immunise all infants at 9 months of age might require revision for premature infants, especially those whose mothers have vaccination-induced immunity.     

Placental pathology and neurological morbidity in preterm infants during the first two weeks after birth

Background

The placenta plays a crucial role during pregnancy and dysfunction causes long-term neurological problems. Identifying placenta-related risks for neurological problems shortly after birth may provide clues for early interventions aiming to improve neurological outcome.

Objective

To determine the association between placental pathology and neurological morbidity in preterm infants during the first two weeks after birth.

Study design

Placentas of 52 singleton, preterm infants (GA: 25–31 weeks, BW: 560–2250 grammes) were examined for histopathology. The infants' neurological condition shortly after birth was determined by assessing the quality of their general movements (GMs): normal, abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS) was also assigned.

Results

Examination of the placentas revealed maternal vascular underperfusion (n = 29), ascending intrauterine infection (AIUI) (n = 19), villitis of unknown aetiology (n = 6), chronic deciduitis (n = 11), foetal thrombotic vasculopathy (FTV) (n = 9), and elevated nucleated red blood cells (NRBCs) as a marker for foetal hypoxia (n = 7). None of the placental lesions were significantly associated with the quality of GMs or MOS.

Conclusions

This study indicated that placental lesions were not associated with infants' neurological condition as measured by the quality of their general movements during the first two weeks after birth.     

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background

Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants.

Objective

To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth.

Study design

Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity.

Results

Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies.

Conclusions

Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.     

Seroepidemiology of varicella-zoster virus in Bangladesh

Data on the seroprevalence of antibodies protective against the varicella-zoster virus are needed to develop strategies to prevent varicella infections in Bangladesh. Of 1209 patients evaluated at referral-level health facilities in Dhaka, 943 (78%) had no known history of chickenpox and were tested by latex agglutination for the presence of varicella-zoster antibody in serum. Forty-one per cent (386) of the 943 specimens tested were negative. Seropositivity was highest among neonates (83%), declined sharply to 19% in those aged 7-12 months, and thereafter rose steadily with age until a plateau of 85% was reached after the age of 16 years. This first report of varicella-zoster antibody seroprevalence in Bangladesh suggests that, as in other tropical areas, a significant proportion of children, adolescents and adults are susceptible. Children aged from 15 months to early adolescence might be the most important group to target with the vaccine currently available. However, to ensure successful immunisation, further, population-based seroprevalence data are needed, as are an assessment of the vaccine's acceptability and the accessibility of the target population. Incomplete coverage of young children could result in delayed acquisition, and, ultimately, in more severe disease.     

Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients

The severity of varicella-zoster virus (VZV) in immunocompromised children, especially in those receiving renal transplants, is well known. However, the use of live attenuated virus vaccine in this population is controversial. This study aimed to: (i) assess the immunization status of pediatric renal transplant recipients at our center; (ii) determine the anti-VZV antibody titers in such patients; (iii) evaluate the response to VZV vaccine in seronegative children and in those who present low antibody titers (defined as <500 mAU/mL).Vaccinated children were monitored for adverse effects for 8 wk after vaccination. Fifty patients with a mean age of 13.7 yr (range, 3-17 yr) were enrolled. In 49, blood samples were collected and antibodies were screened using ELISA. Seropositivity to VZV was found in 43 (88%), and antibody titers were >/=500 mAU/mL in 37 (75.5%). Of the 12 children who were eligible for vaccination and had antibody titers <500 mAU/mL, one developed varicella before vaccination, two did not meet the inclusion criteria, and three parents refused the vaccination. In the six vaccinated children, there were no adverse reactions to the vaccine, and four (66.6%) responded with anti-VZV titers >/=500 mAU/mL 6-8 wk after vaccination. In conclusion, after renal transplantation, varicella vaccine is safe with a 66% rate of conversion to high antibody titers.