Neonatal Immunity Research Articles

Cost-effectiveness of maternal immunization against neonatal invasive Group B Streptococcus in the Netherlands

BackgroundNeonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates. ObjectiveExplore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands. MethodsWe assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017. ResultsUnder base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands. ConclusionsA maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.

Ante-Natal and Post-Natal Influences on Neonatal Immunity, Growth and Puberty of Calves-A Review.

Simple SummaryThe objective of this review is to give the reader an overview of interactions between immunity, growth and puberty in calves and highlight how these influence future performances. The risk of morbidity and mortality is high during the first four weeks of age. Adaption to extra-uterine life starts early during embryonic development and is underpinned by optimal maternal nutrition. It is known that colostrum is paramount to neonate nutrition and passive immunity. Good colostrum management allows the calf to develop coping mechanisms to efficiently utilize feed resources for optimal growth. A deeper understanding of these interactions paves the way for developing strategies to improve immune responses to environmental pathogens, optimal growth and timely attainment of puberty in calves. The literature reviewed here shows that there are opportunities to enhance future performance of cattle paying attention to the interaction of nutrition and immunity at early developmental stages. This then guarantees efficient neonate nutrition and profitable cattle production.Calf immunity, growth and puberty are important factors affecting heifer productivity. The first four weeks of age are critical for reducing calf morbidity and mortality. It is well documented that colostrum is paramount to neonatal nutrition and passive immunity, however, adaptation to extra-uterine life starts early during embryonic development. Therefore, successful calf rearing strategies are underpinned by adequate maternal nutrition during gestation, and good colostrum management. A deeper understanding of these interactions paves the way for developing strategies to improve immune responses to environmental pathogens, optimal growth and timely attainment of puberty in calves. The literature reviewed here shows that there are opportunities to enhance the future performance of cattle paying attention to the interaction of nutrition and immunity at each developmental stage. Therefore, the objective of this review is to give the reader an overview of interactions between immunity, growth and puberty in dairy calves and highlight how these influence future performances.

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury.

Despite the prevalence of preterm brain injury, there are no established neuroprotective strategies to prevent or alleviate mild-to-moderate inflammation-related brain injury. Perinatal infection and inflammation have been shown to trigger acute neuroinflammation, including proinflammatory cytokine release and gliosis, which are associated with acute and chronic disturbances in brain cell survival and maturation. These findings suggest the hypothesis that the inhibition of peripheral immune responses following infection or nonspecific inflammation may be a therapeutic strategy to reduce the associated brain injury and neurobehavioral deficits. This review provides an overview of the neonatal immunity, neuroinflammation, and mechanisms of inflammation-related brain injury in preterm infants and explores the safety and efficacy of anti-inflammatory agents as potentially neurotherapeutics.

The Potential Role of Nonhuman Primate Models to Better Comprehend Early Life Immunity and Maternal Antibody Transfer.

Early life immunity is a complex field of research and there are still gaps in knowledge regarding the detailed mechanism of maternal antibody transfer, the impact of maternal antibodies on infant vaccine responses and the ontogeny of human early life immunity. A comprehensive understanding is necessary to identify requirements for early life vaccines and to improve early childhood immunization. New immunological methods have facilitated performing research in the youngest, however, some questions can only be addressed in animal models. To date, mostly murine models are used to study neonatal and infant immunity since they are well-described, easy to use and cost effective. Given their limitations especially in the transfer biology of maternal antibodies and the lack of infectivity of numerous human pathogens, this opinion piece discusses the potential and prerequisites of the nonhuman primate model in studying early life immunity and maternal antibody transfer.

Monitoring progress of maternal and neonatal immunization in Latin America and the Caribbean

IntroductionThe Americas committed to strengthening maternal and neonatal immunization (MNI) through the Pan American Health Organization (PAHO) Regional Immunization Action Plan (RIAP) 2016–20. We describe the progress toward RIAP MNI-related targets and those related to improvement of data quality and information systems; analyze national MNI policies and vaccination coverages; and identify enablers and challenges of monitoring and reporting MNI vaccination coverage in Latin America and the Caribbean (LAC). MethodologyDescriptive study of national MNI policies, vaccination coverage, and information systems. Sources of information included PAHO–World Health Organization (WHO) / UNICEF Joint Reporting Forms on immunization (JRF) 2013–2019, and other reports. ResultsLAC has met two of three RIAP targets related to MNI (countries with universal hepatitis B birth dose introduction and elimination of maternal and neonatal tetanus) and is on track to meet the other (countries with vaccination of pregnant women). As of 2018, of the 49 countries and territories in LAC, 32 vaccinate pregnant women against influenza and 29 provide tetanus-containing vaccine. Twenty-five countries offer universal hepatitis B birth dose vaccine and 31 offer BCG vaccine. In 2018, regional influenza vaccine coverage among pregnant woman was 75%. Regional coverages for BCG and hepatitis B birth dose (<24 h) vaccines were 93% and 79%, respectively. Countries have exceeded RIAP targets related to the quality of vaccination coverage data and the establishment of electronic immunization registries (EIRs). Challenges in monitoring MNI coverage include estimation of denominators and difficulties disaggregating data by group (e.g., pregnant women versus other groups). ConclusionDespite progress in improving MNI in LAC, countries must further strengthen immunization monitoring systems and data quality to better report vaccination coverage among pregnant women and newborns. EIR and MNI information systems must be integrated, such that countries can use accurate data to design more timely and effective vaccination strategies.

Human CD36hi monocytes induce Foxp3+ CD25+ T cells with regulatory functions from CD4 and CD8 subsets.

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3+ regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3+ T-cell differentiation, the specific antigen-presenting cells required and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14+ monocytes expressing the scavenger molecule, CD36, can generate CD4+ and CD8+ T cells that coexpress Foxp3 and T-bet from both umbilical cord blood. These Foxp3+ T-bet+ T cells potently suppress T-cell proliferation and ameliorate xenogeneic graft-versus-host disease. CD14+ CD36+ monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3+ T cells from both cord blood and adult peripheral naïve T cells. The induction of Foxp3+ T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36hi monocytes may contribute to the peripheral development of Foxp3+ T-bet+ T cells with regulatory functions in both neonates and adults.

Bovine neonate is deficient in innate immunity at birth

With an objective to understand acquisition of innate immunity in bovine neonates, we analyzed perinatal expression of cytokine, adhesion molecule and complement component genes involved in innate and adaptive immune functions. Statistically robust transcriptomic analysis of 27 cytokines showed low IL1B, IL2 and IL7 but high IL23, TGFB1 and TGFB2 expression in bovine neonates post-birth. Unlike mice and humans, no TH2 polarizing cytokine expression occurs in bovine neonates. Further, TH17 and Treg differentiation in bovine neonates may differ from other species like mice and humans. Decreased IL7, IL23R, CXCR3 and increased TGFB1 and TGFB2 expression provides an immunosuppressive environment in the bovine neonate at birth. Transcriptomic analysis of 31 adhesion molecules showed rapid increase in ITGAL expression within a week post-birth in bovine neonates that permits acquisition of innate cytotoxic functions by granulocytes (antibody-mediated), cytotoxic T and NK cells. However, innate immune functions involving phagocytosis and platelet aggregation are deficient in bovine neonates at birth. Of twenty-seven, 18 complement component genes show no significant differential gene expression in neonates post-birth. But low expression of C1QA, C1QB, CQC, C1R and C2 compromises classical and lectin complement pathways mediated lytic function in bovine neonates. The complement-mediated cytotoxic functions, however, normalize between days 7 and 28 post-birth. To conclude, bovine neonate is immunosuppressed and deficient in innate immune competence at birth. Such differences with regard to global innate immune deficiency and lack of TH2 polarization in bovine neonates have profound implications for designing vaccines to prevent neonatal infections. To conclude, species-specific unique characteristics of developing innate and adaptive immune system need to be taken into consideration while designing new immunization strategies to prevent neonatal mortality from infections.

Malaria and Early Life Immunity: Competence in Context.

Childhood vaccines have been the cornerstone tool of public health over the past century. A major barrier to neonatal vaccination is the “immaturity” of the infant immune system and the inefficiency of conventional vaccine approaches at inducing immunity at birth. While much of the literature on fetal and neonatal immunity has focused on the early life propensity toward immune tolerance, recent studies indicate that the fetus is more immunologically capable than previously thought, and can, in some circumstances, mount adaptive B and T cell responses to perinatal pathogens in utero. Although significant hurdles remain before these findings can be translated into vaccines and other protective strategies, they should lend optimism to the prospect that neonatal and even fetal vaccination is achievable. Next steps toward this goal should include efforts to define the conditions for optimal stimulation of infant immune responses, including antigen timing, dose, and route of delivery, as well as antigen presentation pathways and co-stimulatory requirements. A better understanding of these factors will enable optimal deployment of vaccines against malaria and other pathogens to protect infants during their period of greatest vulnerability.

Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves.

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

Empowering traditional birth attendants as agents of maternal and neonatal immunization uptake in Nigeria: a repeated measures design

BackgroundAdequate immunization coverage in rural communities remain a challenge in Nigeria. Traditional birth attendants (TBAs) form an integral part of the social, cultural and religious fabric in most rural communities in Nigeria. Despite their limitations in handling the complications of childbirth, TBAs are widely accepted and patronized, especially in rural areas. The objectives of the project were to empower TBAs and assess the use of a culturally adapted audio-visual workshop intervention to change their knowledge, attitude and willingness to promote immunization uptake.MethodsA repeated-measures design that used a convenience sampling technique to select 90 TBAs from the three geopolitical zones of Imo State, Nigeria. The TBAs were engaged through a culturally adapted audio-visual workshop. Data were collected before and immediately after intervention using a pretested questionnaire. Chi square test was done to determine any significant association with the zone of practice and paired sample t-test analysis to determine any significant pre and post intervention change. Level of significance was set at p ≤ ·05.ResultsMore than half of the TBAs had at most, a secondary level of education (54·4%). The average length of time they practiced as TBAs was 16 years with an average of ten birth deliveries per month. After the intervention, all the respondents (100%) reported a willingness to always promote immunization uptake and also, there was a statistically significant increase in Knowledge (p < ·000). Similarly, the level of knowledge in the post intervention period appeared to be significantly associated with the zone of practice (p = ·027).ConclusionThe workshop intervention empowered the TBAs irrespective of their zones of residence by successfully improving their knowledge, though at varying levels; and consequently, their willingness to always promote immunization uptake.

Innate and humoral immune parameters at delivery in colostrum and calves from heifers experimentally infected with Neospora caninum

Neospora caninum is a leading cause of abortion in cattle worldwide. The study of the immune response against N. caninum is critical to understand its epidemiology, pathogenesis, diagnosis and, ultimately, in preventing and controlling bovine neosporosis. Herein, we determined the gene expression of innate immune components endosomal RNA-sensing TLRs, BMAP28 cathelicidin, TNF-α and IL-10 and characterized the variation in both IgG ratio and avidity at delivery in N. caninum-infected heifers challenged at day 210 of gestation, colostrum and their calves.Increased BMAP28 expression was observed not only in colostrum but also in peripheral blood mononuclear cells (PBMC) and umbilical cord of calves from N. caninum-infected heifers in comparison with mock-infected control group. In addition, statistically significant decrease of TLR7 and IL-10 expression levels were observed in umbilical cord, suggesting an attempt to avoid an exacerbated immune response against the parasite. At delivery, serum and colostrum samples from infected group evidenced specific IgG anti-N. caninum. Infected heifers showed IgG1/IgG2 ratios <1 and high avidity specific IgG. As expected, colostrum samples of these animals exhibited a high IgG1 concentration and elevated avidity values. Three out of four calves from N. caninum-infected heifers had specific IgG with IgG1/IgG2 ratios>1 and lower avidity values before colostrum intake. Interestingly, both IgG1/IgG2 ratios and avidity values increased in seropositive calves after colostrum intake. Overall, this study provides novel information on neonatal immunity in congenitally infected calves, which is essential to understand how the immune pathways could be manipulated or immune components could be employed in order to improve protection against neosporosis.

Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios

Maternally derived antibodies are a key element of neonatal immunity. Understanding the dynamics of maternal antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer can inform neonatal management as well as maternal vaccination strategies. To assess the association between maternal and neonatal SARS-CoV-2-specific antibody concentrations. This cohort study took place at Pennsylvania Hospital in Philadelphia, Pennsylvania. A total of 1714 women delivered at the study site between April 9 and August 8, 2020. Maternal and cord blood sera were available for antibody measurement for 1471 mother/newborn dyads. SARS-CoV-2. IgG and IgM antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed in combination with demographic and clinical data. The study cohort consisted of 1714 parturient women, with median (interquartile range) age of 32 (28-35) years, of whom 450 (26.3%) identified as Black/non-Hispanic, 879 (51.3%) as White/non-Hispanic, 203 (11.8%) as Hispanic, 126 (7.3%) as Asian, and 56 (3.3%) as other race/ethnicity. Among 1471 mother/newborn dyads for which matched sera were available, SARS-CoV-2 IgG and/or IgM antibodies were detected in 83 of 1471 women (6%; 95% CI, 5%-7%) at the time of delivery, and IgG was detected in cord blood from 72 of 83 newborns (87%; 95% CI, 78%-93%). IgM was not detected in any cord blood specimen, and antibodies were not detected in any infant born to a seronegative mother. Eleven infants born to seropositive mothers were seronegative: 5 of 11 (45%) were born to mothers with IgM antibody only, and 6 of 11 (55%) were born to mothers with significantly lower IgG concentrations compared with those found among mothers of seropositive infants. Cord blood IgG concentrations were positively correlated with maternal IgG concentrations (r = 0.886; P < .001). Placental transfer ratios more than 1.0 were observed among women with asymptomatic SARS-CoV-2 infections as well as those with mild, moderate, and severe coronavirus disease 2019. Transfer ratios increased with increasing time between onset of maternal infection and delivery. In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019.

The Fifth International Neonatal and Maternal Immunization Symposium (INMIS 2019): Securing Protection for the Next Generation.

Despite significant progress in reaching some milestones of the United Nations Sustainable Development Goals, neonatal and early infant morbidity and mortality remain high, and maternal health remains suboptimal in many countries. Novel and improved preventative strategies with the potential to benefit pregnant women and their infants are needed, with maternal and neonatal immunization representing effective approaches. Experts from immunology, vaccinology, infectious diseases, clinicians, industry, public health, and vaccine-related social sciences convened at the 5th International Neonatal and Maternal Immunization Symposium (INMIS) in Vancouver, Canada, from 15 to 17 September 2019. We critically evaluated the lessons learned from recent clinical studies, presented cutting-edge scientific progress in maternal and neonatal immunology and vaccine development, and discussed maternal and neonatal immunization in the broader context of infectious disease epidemiology and public health. Focusing on practical aspects of research and implementation, we also discussed the safety, awareness, and perception of maternal immunization as an existing strategy to address the need to improve maternal and neonatal health worldwide. The symposium provided a comprehensive scientific and practical primer as well as an update for all those with an interest in maternal and neonatal infection, immunity, and vaccination. The summary presented here provides an update of the current status of progress in maternal and neonatal immunization.

Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates

BackgroundPregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically.ObjectiveWe characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother.Study DesignWomen who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log2-scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels.ResultsA total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels.ConclusionWe demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies.

Haemoglobin Genotype Status awareness of Some Nursing Parents receiving Neonatal immunization in Jos, North-Central Nigeria

Haemoglobin Genotype Status awareness of Some Nursing Parents receiving Neonatal immunization in Jos, North-Central Nigeria

Transcriptional and functional characterization of neonatal circulating Innate Lymphoid Cells.

Innate lymphoid cells (ILCs), comprising ILC1, 2, and 3 subpopulations, play unique roles in maintaining microbiome homeostasis, mucosal tissue integrity, and control of inflammation. So far, their characterization is dominantly based on tissue‐resident ILCs, whereas little information is available on circulating ILCs, in particular in newborns. In order to get a deeper understanding of neonatal innate immunity, we analyzed the transcriptomes and effector functions of cord blood (CB) ILCs. By RNAseq analysis, all ILC subsets could be clearly distinguished from each other. CB‐derived ILCs were generally closer related to neonatal T than natural killer (NK) cells and several factors shared by all three ILC subsets such as CD28, CCR4, and SLAMF1 are commonly expressed by T cells but lacking in NK cells. Notably, CB ILCs exhibited a unique signature of DNA binding inhibitor (ID) transcription factors (TF) with high ID3 and low ID2 expression distinct from PB‐ or tonsil‐derived ILCs. In vitro stimulation of sorted CB ILCs revealed distinct differences to tissue‐resident ILCs in that ILC1‐like and ILC3‐like cells were nonresponsive to specific cytokine stimulation, indicating functional immaturity. However, CB ILC3‐like cells expressed toll‐like receptors TLR1 and TLR2 and upon stimulation with the TLR2:1 ligand Pam3CSK4, responded with significantly increased proliferation and cytokine secretion. Together, our data provide novel insights into neonatal ILC biology with a unique TF signature of CB ILCs possibly indicating a common developmental pathway and furthermore a role of CB ILC3‐like cells in innate host defense.

The Outcome of Accidental Bacille Calmette-Guérin Overdose During Routine Neonatal Immunization.

We report a retrospective study on outcome of 14 newborn infants who received 62.5 times the recommended dose of Bacille Calmette-Guérin for immunization. All infants then received high-dose isoniazid and rifampicin (20 mg/kg/d each) as preventive therapy for 6 months. All had mild local adverse reactions, a third resolving within 16 weeks and all by 6 months.

Birthweight and Environmental Conditions Impact Skin Barrier Adaptation in Neonates Receiving Natural Oil Massage

Introduction: Skin interventions have been implemented to reduce neonatal mortality, demonstrating the skin’s role in neonatal innate immunity. We examined the impact of birthweight and environmental conditions on skin integrity in infants receiving oil massage in rural Nepal. Methods: In a community-based cluster randomized controlled trial, 991 premature and full-term infants were grouped by birthweight as: (1) 920–1,560 g, (2) 1,570–2,450 g, (3) 2,460–2,990 g, and (4) 3,000–4,050 g and by high or low heat index (HI). Skin integrity was measured as erythema, rash, dryness, pH, protein concentration, and transepidermal water loss (TEWL). Results: Skin pH was higher for the smallest (group 1) than the largest infants (group 4) and higher for group 2 than 3 and 4. Arm and leg rash differed for all 4 groups, with the least amount of rash for the smallest babies. Erythema was lower for group 1 than all others. The lower day 1 values for pH, TEWL and protein at high versus low HI remained lower over 28 days. The pH reduction was faster at high HI. Erythema (arm, leg) was more severe at high HI. Rash severity was greater at high HI for arms and legs every day. Conclusions: Birthweight influenced the skin response to oil massage. The smallest infants had the lowermost skin irritation, suggesting diminished ability to mount an inflammatory response. High HI may be protective for premature infants in low resource settings.

Infant immunity against viral infections is advanced by the placenta-dependent vertical transfer of maternal antibodies

Neonatal passive immunity, derived from transplacental transfer of IgG antibodies from mother to fetus during pregnancy, can mitigate the risk for severe infections in the early postnatal period. Understanding the placenta as the gateway organ in this process, we aimed to evaluate the influence of specific factors modulating the transplacental IgG transfer rate (TPTR) in 141 mother/neonate pairs. We further evaluated the potential health advantage elicited by maternal IgG with regard to respiratory tract infections during infancy and early childhood. Data and biological samples collected within the prospective longitudinal pregnancy cohort study PRINCE (Prenatal Identification of Children’s Health) were used for these analyses. We tested IgG antibody levels against seven pathogens (measles, mumps, rubella, tetanus, diphtheria, pertussis and influenza A) by ELISA and detected seropositivity in 72.6–100% of pregnant women and in 76.3–100% of their neonates, respectively. Cord blood IgG levels reached 137–160% of levels detected in maternal blood. Strikingly, assessment of TPTR for all seven antigens highlighted that TPTR strongly depends on individual placental function. Subsequent in-depth analysis of anti-influenza A IgG revealed a link between cord blood levels and uterine perfusion, measured by uterine artery pulsatility index. Moreover, higher cord blood anti-influenza A IgG levels were associated with a significantly reduced risk for respiratory tract infections during the first six months of life, indicating a high degree of cross-reactivity and possible pathogen-agnostic effects of anti-influenza A antibodies. Taken together, our data suggest that early life immunity is modulated by maternal IgG levels and individual placental features such as perfusion. Vaccination of pregnant women, i.e. against influenza, can increase neonatal antibody levels and hereby protect against early life respiratory infections. Consequently, specific guidelines should evolve in order to safeguard neonates born from pregnancies with poorer placental capacity for vertical transfer of protective antibodies.

NEONATE HEALTH AND CALF MORTALITY IN A DECLINING POPULATION OF NORTH AMERICAN MOOSE (ALCES ALCES AMERICANUS).

Moose (Alces alces americanus) populations in many areas along the southern extent of the North American moose range, including Minnesota, have experienced decline. Ascertaining neonate health and cause-specific mortality is critical where calf survival is low and understanding underlying causes of population dynamics is important. To investigate moose neonate health and causes of mortality, we studied 43 calves shortly after parturition during 2013-15 and 2018. The observed natural calf mortality rate was 84% by the following January of each calving season. Most natural calf mortalities were caused by black bear (Ursus americanus) or wolf (Canis lupus) predation or associated injuries (71%) but also included stillbirth (16%), orphaning (7%), generalized bacterial infection (3%), and hunter harvest (3%). Neonate health was evaluated in 27 calves by hematology, serum biochemistry profile, and maternally derived immunoglobulin. General health parameters were mostly within an expected range for normal health and adequate maternal immunoglobulin transfer. Importantly, these data contribute to a growing body of literature on moose neonate health and is the first report, to our knowledge, of maternally derived immunity in moose neonates.