Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women

BackgroundGroup B Streptococcus (GBS) is the leading cause of life-threatening infections in new-borns and may cause invasive disease, stillbirth and preterm delivery during pregnancy. While no licensed vaccine exists, maternal immunization might protect against neonatal disease and adverse pregnancy outcomes. We assessed the safety and immunogenicity of a prototype vaccine consisting of the fused N-terminal domains of the AlphaC and Rib surface proteins of GBS (GBS-NN).MethodsGBS-NN was tested in a randomised, double-blind, placebo-controlled, parallel group, phase I study, in healthy non-pregnant women. A dose-escalation phase, with two doses, four weeks apart, of 10, 50 or 250 µg, administered with or without aluminium hydroxide, was initially assessed (n = 60). This was followed by a dose-confirmation study, where one dose of 100 µg adjuvanted GBS-NN was compared with two doses of either 50 or 100 µg adjuvanted GBS-NN, again administered with four weeks interval between the doses (n = 180). Safety and immunogenicity were monitored for one year.ResultsGBS-NN was well tolerated with some, mostly mild, injection site reactions observed. Adjuvant significantly increased antibody concentrations and the response was boosted by a second dose. The IgG GMCs remained strongly elevated during the whole one-year duration of the study. Maximal responses occurred after two 50 µg doses, resulting in IgG GMC of 16.9 µg/ml at the primary immunological endpoint, twelve weeks after the first dose. For this regimen, 100% and 89% of the subjects achieved antibody levels above the arbitrary thresholds of 1 and 4 µg/ml, respectively. The added beneficial effect of a second dose was most pronounced for subjects with pre-existing IgG levels below the median of the entire cohort.ConclusionThe prototype GBS-NN vaccine was found to be well tolerated and highly immunogenic with an optimal regimen of two doses of 50 µg in the presence of adjuvant. Further development of a maternal vaccine based on the N-terminal domains of the alpha-like protein family of GBS is warranted (NCT02459262).     

A parallel increase in placental oxidative stress and antioxidant defenses occurs in pre-gestational type 1 but not gestational diabetes

We aimed to determine the oxidative stress status in placentas obtained from gestational (GDM) and type 1 (T1D) diabetic pregnancies. Malonaldehyde and protein carbonyls, two biomarkers of oxidative damage, were higher in T1D but not in GDM placentas. Also, higher reduced glutathione and lower oxidized glutathione levels and higher glutathione peroxidase activity were found in T1D but not in GDM placentas. These results suggest that T1D placentas may develop a protective antioxidant mechanism to overcome higher oxidative stress levels.     

Monitoring of human cytomegalovirus DNAemia during primary infection in transmitter and non-transmitter mothers

Background and objectivesIt has been reported that maternal DNAemia is detectable in three quarters of pregnant women with acute/recent primary HCMV infections, with a higher median number of HCMV DNA copies/ml blood in transmitter as compared with non-transmitter mothers.Study designThe kinetics of HCMV DNA in blood of transmitter vs non-transmitter pregnant women with primary HCMV infection was retrospectively analyzed from their first blood sampling at referral up to amniocentesis strictly performed at 19–21 weeks’ gestation. Monthly monitoring of maternal HCMV DNAemia was performed up to prenatal diagnosis.ResultsHCMV DNAemia was determined in 154 pregnant women. At amniocentesis, HCMV DNA in blood was positive in 42/50 (84.0%) amniotic fluid (AF) −positive and 21/104 (20.2%) AF-negative mothers (p < 0.0001). The number of HCMV DNA copies/ml blood was not significantly different in AF-positive as compared with AF-negative mothers in the interval 0–30 days post-infection (p = 0.14). On the contrary, HCMV DNA load at 30–60 days (p = 0.03) and at 60–90 days (p < 0.001) after onset of infection was significantly different, as observed at amniocentesis (p < 0.001). Three patterns (clearance, delayed decrease, and increasing) in both transmitter and non-transmitter mothers were observed. However, 79.8% AF- negative mothers cleared HCMV DNA in blood, while in AF-positive mothers increasing (44.0%) or persisting (40.0%) levels of DNAemia were observed.ConclusionsThe presence of viral DNA in maternal blood at amniocentesis is statistically associated with fetal HCMV infection. Increasing or persisting levels of maternal DNAemia during primary HCMV infection in pregnancy correlate with HCMV transmission to the fetus.     

Hématome rétroplacentaire. Diagnostic,prise en charge et pronostic maternofœtal : étude rétrospective de 100 cas

ObjectivesTo update knowledge on placental abruption because there are few recent series published although the perinatal care has progressed.Patients and methodsA retrospective observational study has been conducted on 100 consecutive cases of abruptio placentae, occurring from January 2008 to June 2011, in the two maternity units of the University Hospital of Strasbourg (France).ResultsOne hundred and five births among which five twin pregnancies were included. Clinical context was evident in 91% of cases, but the classic clinical triad was present in only 4% of cases. Clots were found at immediate placenta examination in 77% of cases. Pathological diagnosis was directly in accordance with clinical diagnosis in half the cases. Mean date of childbirth was 33 weeks of amenorrhea and 6 days. Sixty-seven patients gave birth prematurely. Among them, 50 patients delivered before 34 weeks. Sixty caesareans were performed in emergency before labor, including 47 with general anesthesia. Twelve patients had post-partum haemorrhage and ten coagulation disorders. There was no maternal death. Perinatal mortality was 19% with 13 fetal deaths in utero (12.4%), four children born in an apparent death state with resuscitation failure (3.8%) and three neonatal deaths (2.8%).Discussion and conclusionPlacental abruption is a serious and unpredictable situation. Joint medical care of obstetricians and intensivists is often required. Perinatal mortality mainly occurs in utero.     

Maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media

A randomized trial of an investigational 9-valent pneumococcal conjugate vaccine (PCV-9) or placebo given to pregnant women during the last trimester to prevent early infant otitis media (OM) was conducted. All infants received Prevnar^® at 2, 4, 6, and 12 months. Clinic and adverse event records were reviewed to identify OM. Variables significantly related to acute OM by age 6 months (p < 0.05) were: vaccine group (9 valent or placebo), sibling history of tympanostomy tubes, upper respiratory infection, and number of clinic visits by 6 months. Infant OM rates were similar between 6 and 12 months (58% and 56%). Results suggested that immunizing pregnant women with PCV-9 increased infants’ risk of acute OM in the first 6 months of life, and this correlated with decreased infant antibody responses to their infant Streptococcus pneumoniae vaccine serotypes, but did not influence antibody responses to 3 other serotypes two of which were in maternal vaccine (types 1 and 5) and one was a control (type 7F). Explanations for these results include dampening of infant antibody production by high levels of passively acquired maternal pneumococcal antibodies and/or altered B lymphocyte immune responses in infants exposed to these specific polysaccharide antigens in utero.     

Maternal Attitudes and Behaviors Regarding Feeding Practices in Elementary School−Aged Latino Children: A Pilot Qualitative Study on the Impact of the Cultural Role of Mothers in the US−Mexican Border Region of San Diego,California

This study aimed to explore the attitudes and behaviors of Latino mothers around feeding their children. Using qualitative methods, we conducted four focus groups in Spanish with 41 Latino mothers of elementary school-age children in San Diego County, CA. Latino mothers' mean age was 41 years; 90% were foreign-born; and 74% had a high school education or less. We explored cultural viewpoints around feeding and cooking and feeding strategies used. Focus groups were analyzed based on a priori and emergent themes. The following themes around feeding emerged: feeding attitudes central to the maternal responsibility of having well-fed children and feeding behaviors that centered on cooking methods, supportive behaviors, and reinforcement strategies for “eating well.” These findings increase our understanding of the Latino maternal role to feed children and can help to inform more culturally appropriate research to effectively address nutritional issues and obesity prevention in Latino children.