Developmental,behavioral, and pharmacological characteristics of rat offspring from mothers receiving ethanol during gestation or lactation

Ethanol solution (10 or 20% v/v) sweetened with .4% saccharin was given to female rats as the only source of fluid. In the 1st experiment the administration was throughout the gestation period. Developmental, behavioral, and pharmacological tests were performed with the offspring. Litters born from females of the experimental group showed a decrease in the mortality rate induced by pentylenetetrazol, in comparison with either pair-fed controls or an ad libitum control group. No other differences were detected. In the 2nd experiment the administration was throughout the lactation period. Pups raised by lactating mothers receiving ethanol showed a significant decrease in weight gain. Also, the maternal behavior of the ethanol-treated mothers, measured by nest-building and retrieval activities, showed a significant decrease when compared to pair-fed controls.     

Failure of malaria vaccination in mice born to immune mothers.

Female BALB/c mice were vaccinated against blood stage P. yoelii (17XL strain), infected 2 weeks later and after recovery mated to normal C57B1/6 males. Control matings were with normal BALB/c females. The (C57B1/6 x BALB/c)F1 progeny were vaccinated at 4, 6, 8 or 10 weeks of age and infected 2 weeks later with lethal P. yoelii. All control mice were fully protected, but in the offspring of immune mothers mortality was 100, 87, 50, and 0% respectively. Mice in which the protective effect of vaccination had been abolished showed greatly reduced specific IgG and delayed hypersensitivity (DH) responses to challenge with parasite antigen. Results indicate that this failure of vaccination is due to the transmission of maternal IgG to the offspring which acts to suppress both priming by the vaccine and the generation of specific T helper cells involved in IgG production, as measured by the response to TNP-P. yoelii.     

Sexual differentiation of offspring of mothers treated with cortisone during pregnancy

Treatment of pregnant rats with hydrocortisone (1.5 or 3.0 mg) from Day 14 after conception until birth resulted in shortened anogenital distance and lowered testis weight in male offspring. No changes were found in female anogenital distance. It was concluded that corticosteroids, like stress, during pregnancy causes demasculinization of the male offspring     

Normal aging of offspring mice of mothers with induced inflammation during pregnancy

Intrauterine inflammation is a major risk for offspring neurodevelopmental brain damage and may result in cognitive limitations and poor cognitive and perceptual outcomes. In the present study we tested the possibility that prenatal exposure to a high level of inflammatory factors may increase the risk for neurodegeneration in aging. The effect of systemic maternal inflammation (MI), induced by lipopolysaccharide (LPS) on offspring brain aging, was examined in 8 month old (adult) and 20 month old (aged) offspring mice. A significant effect of age was found in the distance and velocity of exploration in the open field in both groups. In addition, MI aged offspring covered longer distances and enter frequently to the center of the field compared with the aged control group. Although only little difference was found in the aged MI offspring compared with the control offspring, the overall profile of behavior of these mice differs from that of the control group, as detected by clustering analysis. The expression of the death-associated protein FAS-ligand and the amount of apoptotic cell death were examined in the brains of aged offspring. Similar levels of FAS-ligand expression and parallel density of apoptotic cells were detected in the brains of aged mice of control and MI groups. Altogether, moderate systemic MI was not found to increase the risk for cell death in the aged offspring; limited effect was found in mice profile of behavior.     

TTV infection in children born to mothers infected with TTV but not with HBV, HCV, or HIV

The TT virus (TTV) was isolated recently from the serum of a patient with post-transfusion hepatitis. TTV infection is widespread in the general population, and its prevalence increases continuously with age. The pathogenic role of TTV in liver disease remains controversial, and the source of transmission is still unclear. We investigated the pathogenicity and epidemiology of TTV infection in infants born to TTV DNA-positive mothers. Enrolled in this study were 22 mother-child pairs testing negative for antibodies to hepatitis B, hepatitis C, and the human immunodeficiency viruses (HIVs). The children were followed for 30 months after birth. Serum TTV DNA was detected by N22-PCR, and the PCR products were cloned and sequenced. The prevalence of TTV infection in children increased with age. Of the 22 children, 13 (59%) became positive for TTV DNA during the follow-up period. Of these 13 children, 6 (46%) had elevated levels of serum alanine aminotransferase (ALT), although the elevations were transient and mild. TTV viremia was not associated significantly with the abnormal ALT levels. Children with TTV viremia developed neither severe liver disease nor fulminant hepatitis. Phylogenetic analysis showed that, in 11 (85%) of the 13 pairs, the mother and child had the same genotype at the first PCR-positive time point. Among those 11 mother-child pairs, 6 (55%) had identical TTV nucleotide sequences. However, the genotype of predominant clones changed in 5 (50%) of 10 children who were positive for TTV DNA at two or more time points during the follow-up period. In conclusion, this study did not provide evidence that TTV infection is related to liver disease in children. Although the main source of TTV infection in children is presumed to be their mothers, transmitted via non-parenteral routes in the course of daily contact, intrafamilial carriers may also be sources of TTV infection.     

Protected Trypanosoma cruzi infection in rats born to mothers receiving interferon-gamma during gestation is associated with a decreased intramacrophage parasite growth and preferential synthesis of specific IgG2b antibodies

We demonstrated that administration of interferon gamma (IFN-gamma) to pregnant rats conferred partial resistance in their offspring to further challenge with Trypanosoma cruzi. Because of the effects of IFN-gamma on macrophage activation and immunoglobulin isotype selection, offspring were now studied to ascertain whether this intervention modifies the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (PE), together with the anti-T. cruzi IgG isotypes. To evaluate the possibility of a detrimental effect of IFN-gamma, serum levels of anti-sulphatide autoantibodies were also investigated. Offspring were born to mothers undergoing one of the following procedures during gestation: treatment with recombinant rat IFN-gamma, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating; infection with 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group; the same protocol except that physiological saline was injected instead of IFN-gamma; injection of physiological saline only. Offspring were challenged at weaning with a similar dose of T. cruzi, to constitute four groups of infected young, plus an additional group of age-matched uninfected rats born to control mothers. PE were harvested at day 7 postinfection (pi), exposed to parasites and further investigated for the replication of T. cruzi and NO production, whereas ELISA studies for measuring serum anti-T. cruzi IgG subclasses and anti-sulphatide autoantibodies were performed at day 30 pi. The number of intracellular parasites in PE was markedly decreased in young born to IFN-gamma-treated mothers, this not being accompanied by higher nitrite levels in culture supernatants. Offspring delivered by IFN-gamma-treated mothers showed no higher serum concentrations of anti-sulphatide autoantibodies, but exhibited a preferential synthesis of anti-T. cruzi IgG2b antibodies. This rat isotype is known to fix complement and constitutes the rat counterpart of IgG2a mouse immunoglobulins whose synthesis is favoured by IFN-gamma.     

Markers of hepatitis-viral infection in children born of mothers with hepatitis B

Sixty-two women suffering from hepatitis B (HB) and their newborn babies were examined by a highly sensitive radioimmunoassay (RIA). The fluorescent antibody technique was also used to examine autopsy specimens of livers of 7 fetuses, 1 stillborn, and 3 babies dying in the first days of life whose mothers during pregnancy or delivery had experienced HB. Frequent infection of babies (77.8%) was observed at high concentrations of HBsAg in mothers in labor with subsequent development of persisting HBs-antigenemia, and in half of the babies of chronic hepatitis. HBsAg was detected in the first days of life not only in the blood serum, but also in the liver tissue which may be explained by intrauterine infection. At low concentrations of HBsAg in mothers the babies were infected less frequently (26.1%) and half of them were shown to have anti-HBs in the umbilical blood and blood serum in the first days and months of life. Anti-HBc transmission from mothers was also demonstrated. In babies born to convalescents after HB in the absence of HBsAg, anti-HBs in combination with anti-HBc were determined.     

Susceptibility of neonate mice born to Schistosoma mansoni-infected and noninfected mothers to subsequent S. mansoni infection

The present study tested the hypothesis that prenatal exposure of neonate Outbred albino mice to Schistosoma mansoni antigens (Ags) or antibodies (Abs) modulates their immunity against postnatal responses to infection. Persistence of maternal S. mansoni Abs and/or Ags in mice born to S. mansoni-infected mothers (IF-IMs) and noninfected mothers (IF-NMs) for up to 8 weeks after delivery was investigated. A higher level of anti-S. mansoni IgG Ab was detected in sera of 1-week-old mice born to IF-IM compared to controls. Then, immunoglobulin (Ig)G gradually decreased to the eight week. No anti-S. mansoni IgM Ab was detected in sera of these offspring at any week after delivery. Schistosoma Ags were detected in liver and kidney tissues of mice born to infected mothers. However, Ags decreased markedly till the sixth week in the liver but increased significantly at the sixth week in the kidney. Eight-week-old mice born to infected and noninfected mothers were infected with 200 S. mansoni ceracriae. Their sera and livers were collected for testing IgG and granuloma formation 6 weeks postinfection. Worms were collected via portal perfusion and counted. Anti-S. mansoni IgG level, size and number of liver granuloma, and worm burden were significantly reduced in the offspring of infected mothers. These data suggest that in utero exposure of Outbred albino mice to S. mansoni may attenuate the pathogenesis of S. mansoni in subsequent challenge.     

Suppression of follicular trapping of antigen-antibody complexes in mice treated with anti-IgM or anti-IgD antibodies from birth

Mice were treated from birth with either goat anti-mouse IgM or with a monoclonal anti-IgD antibody. When they were 8 weeks old, cohorts of these mice were given 125I-labelled antigen, either by itself, or in an antigen-antibody complex. Anti-IgM-treated mice, which did not develop follicular structures in their spleens, failed to retain immune complexes on follicular dendritic cells in the characteristic pattern. Anti-IgD-treated mice, which had small follicles consisting of IgM+ IgD- B cells in their spleens, retained substantially smaller amounts of immune complexes than normal. These results support the concept that B lymphocytes transport antigen-antibody complexes to follicular dendritic cells. Furthermore, in the mouse it seems likely that this is mediated by both IgM+ IgD+ and IgM+ IgD- B cells.     

Treatment with sildenafil prevents impairment of learning in rats born to pre-eclamptic mothers

Pre-eclampsia is an important hypertensive pregnancy disorder and a main cause of maternal and fetal morbidity and mortality. Children born from mothers with pre-eclampsia may present cognitive deficits. The mechanisms leading to this cognitive impairment remain unclear and no treatments to improve it have been tested. Pre-eclampsia is associated with impaired regulation of the nitric oxide-3‵-5‵guanosine monophosphate cyclic (cGMP) pathway, which modulates some cognitive functions. We hypothesized that alterations in the NO-cGMP pathway would be involved in the mechanisms leading to cognitive impairment in rats born to pre-eclamptic mothers and that treatment with sildenafil, an inhibitor of the phosphodiesterase that degrades cGMP, could restore their cognitive function. To test these hypotheses, we used an animal model of pre-eclampsia in rats: pregnant rats treated with l-nitro-arginine methyl ester, an inhibitor of nitric oxide synthase. Using this model, we assessed: (1) whether rats born to pre-eclamptic mothers show reduced learning ability and/or altered motor activity or coordination when they are 2 months-old; (2) whether cognitive impairment is associated with reduced function of the glutamate-NO-cGMP pathway in brain in vivo; and (3) whether treatment of the mothers with sildenafil prevents this cognitive and motor alterations. The results reported show that the ability to learn a conditional discrimination task in a Y maze is reduced in rats born to pre-eclamptic mothers. This impairment was associated with reduced function of the glutamate-NO-cGMP pathway in brain in vivo, as assessed by microdialysis in freely moving rats. Treatment with sildenafil restores the function of this pathway and learning ability.     

Hepatitis B vaccine alone or in combination with anti-HBs immunoglobulin in the perinatal prophylaxis of babies born to HBsAg carrier mothers.

The efficacy of hepatitis B virus (HBV) vaccine alone (group I) or in combination with hepatitis B immunoglobulin (HBIG) (group II) for prevention of perinatal transmission of the virus was assessed in 21 and 24 neonates, respectively. 58 infants who could not be vaccinated constituted the control group. It was observed that in the unvaccinated group approximately 70% of the infants became infected. In both the vaccinated groups, the seroconversion and seroprotection rates (anti-HBs > or = 10 IU/1) were almost similar at 6 months of follow up, but, at 12 months, infants given HBIG and vaccine showed better seroprotection rate (85%) than those given vaccine alone (58.8%). Immune response to the vaccine was also better in both the groups if the mothers were anti-HBe positive. Despite immunization, 14.2% and 25% infants in group I and II, respectively, became chronic carriers if their mothers were HBeAG positive.     

Anthropometric charts for infants with trisomies 21, 18, or 13 born between 22 weeks gestation and term: the VON charts

Data on birth weight for gestational age (GA) are not well described for infants with trisomy 21 (T21), trisomy 18 (T18), or trisomy 13 (T13). We report on anthropometric charts of infants with these conditions using data from the Vermont Oxford Network (VON). Data from a total of 5,147 infants with T21 aged 22-41 weeks, 1,053 infants with T18 aged 22-41 weeks, and 613 infants with T13 aged 22-40 weeks were used to create birth weight for GA charts. Head circumference for GA charts were created for infants with T21 only. Combined-sex charts were generated for infants with T18 or T13 while sex-specific charts were generated for infants with T21. Smoothed centiles were created using LmsChartMaker Pro 2.3. Among the three examined groups, infants with T18 were the most likely to be growth restricted while infants with T21 were the least likely to be growth restricted. The new charts for infants with T21 were also compared to the Lubchenco and Fenton charts and both show frequent misclassification of infants with T21 as small or large for GA. The new charts should prove to be useful, especially for infants with T21, to assist in medical management and guide nutrition care decisions.     

Susceptibility to Pneumocystis carinii infection: host responses of neonatal mice from immune or naive mothers and of immune or naive adults.

Mice from either naive or immunized dams were given intranasal inoculations of Pneumocystis carinii as neonates (24 to 48 h old). Lung P. carinii burdens increased through day 13 postinoculation in all pups and declined to nearly undetectable numbers by day 23 in pups from immune mothers. However, P. carinii numbers in pups from naive mothers did not begin to decline significantly until after day 33, and P. carinii organisms were still detectable in low numbers through day 45. In contrast, the lungs of naive or immunized adult mice contained detectable numbers of P. carinii organisms only up to 9 or 3 days, respectively, after inoculation. The onset of clearance of P. carinii organisms from the lungs of neonatal mice and naive adults was coincident with infiltration of neutrophils and CD4+ CD45RBlo cells into the alveolar spaces and increased titers of P. carinii-specific antibody in sera. Immunized dams had high levels of P. carinii-specific antibody in both their sera and milk, and pups from these dams had higher titers of P. carinii-specific antibody than did pups from naive dams. These data indicate that P. carinii survives for a much longer period in neonates than in adult mice, which is the result of a delay in the onset of the immune response in neonates. Furthermore, immunized mothers contributed to an early clearance of P. carinii organisms by their offspring presumably because of the transfer of P. carinii-specific antibody. However, the passively acquired antibody did not seem to have an effect until the neonates began to mount their own responses.