Maternal Immunization Research Articles

Assessing the feasibility of passive surveillance for maternal immunization safety utilizing archival medical records in Kinshasa, Democratic Republic of the Congo

IntroductionSince the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC). MethodsA retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence. ResultsA total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest. ConclusionsArchival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus Vaccination in Pregnancy: Implications for Maternal and Infant Immunity.

BackgroundSARS-CoV-2 infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus.MethodsWe measured Spike-specific immunoglobulin G (anti-S IgG) and A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in two academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity.ResultsThe study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P) and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation (VAX-L). VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (p < .0001), while INF mothers had higher BM: serum anti-S IgA ratios compared to VAX mothers (p = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (p < 0.0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, p = 0.013), but not infection.ConclusionsBNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S Ig, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM Ig production. Next generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Gut microbiota-reactive IgG regulates gut microbiota development and immunity against enteric pathogens in early life

Abstract The gut microbiota elicits antigen-specific IgG at steady state that cross-reacts to pathogenic Gram-negative Enterobacteriaceae to confer protection against systemic infection. The role of these IgG antibodies in the development of gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we demonstrate that gut microbiota-induced maternal IgG is transferred to the neonatal gut through maternal milk via the neonatal Fc receptor and confers critical protection by inhibiting colonization and attachment of C. rodentium to the mucosa in the neonatal gut. Enhanced neonatal immunity against oral C. rodentium infection was observed following maternal immunization with a gut microbiota-derived IgG antigen, outer-membrane protein A (OMP-A), or induction of protective IgG antibodies in germ-free mice after reconstitution with IgG-inducing gut bacteria. Furthermore, we generated a mouse model with complete deficiency in all IgG isotypes. IgG-deficient neonatal mice exhibited increased susceptibility to C. rodentium infection, altered gut microbiome and increased numbers of intestinal IL-17-producing γδ T cells driven by the gut microbiome at steady state. The altered gut microbiome persisted into adulthood in IgG KO mice and contributed to increased disease severity in DSS-induced colitis. Taken together, our studies have defined critical roles for gut microbiome-induced IgG antibodies in shaping the gut microbiome and immunity against Gram-negative enteric pathogens from early life to adulthood.

Inflammatory responses to Listeria monocytogenes infection in the placenta

Abstract The immunological defense of the developing fetus is crucial for a successful pregnancy. The placenta plays key roles in protecting the fetus against rejection by the maternal immune system, while it ensures its defense against most pathogens. The mechanisms that orchestrate the placental immune functions are still poorly understood. The bacterial pathogen Listeria monocytogenes (Lm) breaches the maternal/fetal barrier, infects the placental chorionic villi, and reaches the fetus resulting in poor pregnancy outcomes. We studied the interplay between Lm and key players of the placental antimicrobial defense: trophoblasts (TCs), which are epithelial cells covering placental chorionic villi at the maternal/fetal interface, and placental macrophages (Hofbauer cells, or HBCs), which are the only leukocytes residing in chorionic villi. Both cell types form a critical immune barrier protecting the fetus from infection. We isolated human primary TCs and HBCs from healthy term placentas to study the Lm intracellular lifecycle as well as the cellular responses to infection (RNAseq and cytokine arrays). We found that both cell types were permissive to Lm infection and mounted a pro-inflammatory response to the pathogen including HBCs repolarization towards a pro-inflammatory phenotype favoring the innate immune responses. However, consistent with their placental homeostatic functions, TCs and repolarized HBCs maintained the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity. We will discuss our published studies (PMID 34399615 and 34367171) and recent data that teased apart the role of the Lm virulence factors in the inflammatory responses of placental cells. Supported by NIH (R01AI157205, R21AI105588, R03AI149371)

PL5.4 (Gusdon Award Finalist): Defining maternal decidual immunity and the developmental consequences of Zika virus infection during first‐trimester pregnancy

PL5.4 <i>(Gusdon Award Finalist)</i>: Defining maternal decidual immunity and the developmental consequences of Zika virus infection during first‐trimester pregnancy

RSV Prevention in All Infants: Which Is the Most Preferable Strategy?

Respiratory syncytial virus (RSV) causes a spectrum of respiratory illnesses in infants and young children that may lead to hospitalizations and a substantial number of outpatient visits, which result in a huge economic and healthcare burden. Most hospitalizations happen in otherwise healthy infants, highlighting the need to protect all infants against RSV. Moreover, there is evidence on the association between early-life RSV respiratory illness and recurrent wheezing/asthma-like symptoms As such, RSV is considered a global health priority. However, despite this, the only prevention strategy currently available is palivizumab, a monoclonal antibody (mAb) indicated in a subset of preterm infants or those with comorbidities, hence leaving the majority of the infant population unprotected against this virus. Therefore, development of prevention strategies against RSV for all infants entering their first RSV season constitutes a large unmet medical need. The aim of this review is to explore different immunization approaches to protect all infants against RSV. Prevention strategies include maternal immunization, immunization of infants with vaccines, immunization of infants with licensed mAbs (palivizumab), and immunization of infants with long-acting mAbs (e.g., nirsevimab, MK-1654). Of these, palivizumab use is restricted to a small population of infants and does not offer a solution for all-infant protection, whereas vaccine development in infants has encountered various challenges, including the immaturity of the infant immune system, highlighting that future pediatric vaccines will most likely be used in older infants (>6 months of age) and children. Consequently, maternal immunization and immunization of infants with long-acting mAbs represent the two feasible strategies for protection of all infants against RSV. Here, we present considerations regarding these two strategies covering key areas which include mechanism of action, “consistency” of protection, RSV variability, duration of protection, flexibility and optimal timing of immunization, benefit for the mother, programmatic implementation, and acceptance of each strategy by key stakeholders. We conclude that, based on current data, immunization of infants with long-acting mAbs might represent the most effective approach for protecting all infants entering their first RSV season.

Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden

SummaryBackgroundGroup B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets.MethodsWe collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates.FindingsData from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9–21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100–455 000) early-onset and 162 200 (70 200–394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800–187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500–125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600–96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500–66 200) maternal iGBS cases and 46 200 (20 300–111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births.InterpretationOur analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies.FundingBill & Melinda Gates Foundation.

Boosting maternal and neonatal humoral immunity following SARS-CoV-2 infection using a single messenger RNA vaccine dose

BackgroundPost–COVID-19 vaccine boosting is a potent tool in the ongoing pandemic. Relevant data regarding this approach during pregnancy are lacking, which affects vaccination policy guidance, public acceptance, and vaccine uptake during pregnancy. We aimed to investigate the dynamics of anti–SARS-CoV-2 antibody levels following SARS-CoV-2 infection during pregnancy and to characterize the effect of a single postinfection vaccine booster dose on the anti–SARS-CoV-2 antibody levels in parturients in comparison with the levels in naïve vaccinated and convalescent, nonboosted parturients.Study DesignSerum samples prospectively collected from parturients and umbilical cords at delivery at our university-affiliated urban medical center in Jerusalem, Israel, from May to October 2021, were selected and analyzed in a case-control manner. Study groups comprised the following participants: a consecutive sample of parturients with a polymerase chain reaction–confirmed history of COVID-19 during any stage of pregnancy; and comparison groups selected according to time of exposure comprising (1) convalescent, nonboosted parturients with polymerase chain reaction–confirmed COVID-19; (2) convalescent parturients with polymerase chain reaction–confirmed COVID-19 who received a single booster dose of the BNT162b2 messenger RNA vaccine; and (3) infection-naïve, fully vaccinated parturients who received 2 doses of the BNT162b2 messenger RNA vaccine. Outcomes that were determined included maternal and umbilical cord blood anti–SARS-CoV-2 antibody levels detected at delivery, the reported side effects, and pregnancy outcomes.ResultsA total of 228 parturients aged 18 to 45 years were included. Of those, samples from 64 were studied to characterize the titer dynamics following COVID-19 at all stages of pregnancy. The boosting effect was determined by comparing (1) convalescent (n=54), (2) boosted convalescent (n=60), and (3) naïve, fully vaccinated (n=114) parturients.Anti–SARS-CoV-2 antibody levels detected on delivery showed a gradual and significant decline over time from infection to delivery (r=0.4371; P=.0003). Of the gravidae infected during the first trimester, 34.6% (9/26) tested negative at delivery, compared with 9.1% (3/33) of those infected during the second trimester (P=.023). Significantly higher anti–SARS-CoV-2 antibody levels were observed among boosted convalescent than among nonboosted convalescent (17.6-fold; P<.001) and naïve vaccinated parturients (3.2-fold; P<.001). Similar patterns were observed in umbilical cord blood. Side effects in convalescent gravidae resembled those in previous reports of mild symptoms following COVID-19 vaccination during pregnancy.ConclusionPostinfection maternal humoral immunity wanes during pregnancy, leading to low or undetectable protective titers for a marked proportion of patients. A single boosting dose of the BNT162b2 messenger RNA vaccine induced a robust increase in protective titers for both the mother and newborn with moderate reported side effects.

COVID-19 Vaccine Hesitancy during the Perinatal Period: Understanding Psychological and Cultural Factors to Improve Care and Address Racial/Ethnic Health Inequities.

COVID-19 Vaccine Hesitancy during the Perinatal Period: Understanding Psychological and Cultural Factors to Improve Care and Address Racial/Ethnic Health Inequities.

Ex vivo activated CD4+ T cells from young calves exhibit Th2-biased effector function with distinct metabolic reprogramming compared to adult cows

As maternal passive immunity wanes at 6–8 weeks, young calves must rely on their own naïve and developing immune system for protection against pathogens. Typically, an infection in the young induces a T cell-mediated response, which skews towards a Th2 phenotype and results in a reduced effector response. Our study examines the implications this transitional period of immunocompetency has on cellular metabolism in young calves, focusing on effector function of CD4+ T cells in comparison to those from adult cows. Results from sorted CD4+ T cells from young calves and adult cows activated by α-CD3:α-CD28, show that young calves exhibit a significantly greater propensity to produce the Th2 cytokine, IL-4, in comparison to IFN-γ. Concomitantly, cells from young calves and adult cows exhibit no statistical difference in cell surface marker expression induced by α-CD3:α-CD28 stimulation. Metabolically, activated CD4+ T cells from young calves show significantly greater utilization of mitochondrial respiration, measured by oxygen consumption rate (OCR), and greater glycolytic reserve, measured by extracellular acidification rate (ECAR). However, adult cows have a significantly higher change in glycolytic rate after α-CD3:α-CD28 stimulation compared to young calves. Further, CD4+ T cells from young calves have an increased mRNA expression signature associated with glycolytic metabolism (GAPDH, HK2, FBP1, HIF1A) and Th2-associated metabolic signaling (RPTOR) in comparison to adult cows. The distinct metabolic phenotype and associated gene expression in activated CD4+ T cells may be intrinsic drivers of the Th2-biased response by young calves. Additionally, CD4+ recent thymic emigrant cells (RTEs) may further contribute to altered effector function, as they are preferential precursors to Tregs, and based on the microenvironment, have the propensity to polarize toward Th2. Evaluation of T cell master transcription regulators, as well as measuring signal joint T cell receptor excision circles between young calves and adult cows, we observed a significantly increased proportion of RTEs from sorted CD4+ T cells. In this study, we show a unique metabolic profile exhibited by activated CD4+ T cells from young calves in which mitochondrial respiration and glycolytic capacity is significantly increased compared to adult cows.

Operational lessons learned in conducting an international study on pharmacovigilance in pregnancy in resource-constrained settings: The WHO Global Vaccine safety Multi-Country collaboration project

The WHO Global Vaccine Safety Multi-Country Collaboration study on safety in pregnancy aims to estimate the minimum detectable risk for selected perinatal and neonatal outcomes and assess the applicability of standardized case definitions for study outcomes and maternal immunization in low- and middle-income countries (LMICs). This paper documents the operational lessons learned from the study.A prospective observational study was conducted across 21 hospitals in seven countries. All births occurring at sites were screened to identify select perinatal and neonatal outcomes from May 2019 to August 2020. Up to 100 cases per outcome were recruited to assess the applicability of standardized case definitions. A multi-pronged study quality assurance plan was implemented. The impact of the COVID-19 pandemic on site functioning and project implementation was also assessed.Multi-layered ethics and administrative approvals, limited clinical documentation, difficulty in identifying outcomes requiring in-hospital follow-up, and poor quality internet connectivity emerged as important barriers to study implementation. Use of electronic platforms, application of a rigorous quality assurance plan with frequent interaction between the central and site teams helped improve data quality. The COVID-19 pandemic disrupted data collection for up to 6 weeks in some sites.Our study succeeded in establishing an international hospital-based surveillance network for evaluating perinatal and neonatal outcomes using common study protocol and procedures in geographically diverse sites with differing levels of infrastructure, clinical and health-utilization practices. The enhanced surveillance capacity of participating sites shall help support future pharmacovigilance efforts for pregnancy interventions.

Are SARS-CoV-2 Antibodies Detectable in Human Milk After Vaccination Against COVID-19?

BackgroundHuman milk (HM) permits transfer of immunity against infections to infants via bioactive factors. The role of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in HM is poorly understood [1, 2]. This study evaluated SARS-CoV-2 antibodies in the HM of vaccinated healthcare workers (HCW).Methods and ResultsThis prospective study of 122 HCWs was performed from February to April 2021 at the Hospital Universitario Nuestra Señora de Candelaria. Immunoglobulin G (IgG) against nucleocapsid protein and IgG, immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies against spike 1 protein receptor-binding domain against SARS-CoV-2 (anti-SARS-CoV-2 RBD-S1) were analyzed. Unvaccinated breastfeeding mothers without COVID-19 were the control group.The 98 vaccinated participants underwent serum and HM evaluation 14 days after receiving 2 doses of either BNT162b2 mRNA (94%) or mRNA-1273 (6%) coronavirus disease 2019 (COVID-19) vaccines. The mean SARS-CoV-2 RBD-S1 IgG serum concentration was 3379.64 binding antibody units (BAUs)/mL with neutralizing antibody titers >560.9 BAUs/mL. Serum SARS-CoV-2 antibodies in the 24 unvaccinated participants were negative. The HM from vaccinated participants had anti-SARS-CoV-2 RBD-S1 IgG with a mean of 12.19 BAUs/mL compared to 0.02 BAUs/mL (P < .001) in HM from unvaccinated participants. Anti-SARS-CoV-2 S1 IgA was noted in 89% of HM from vaccinated women; no anti-SARS-CoV-2 S1 IgM was detected.A positive correlation was reported between anti-SARS-CoV-2 RBD-S1 IgG in serum and HM (r = 0.36; P < .001). This association was stronger if breastfeeding had been <24 months (r = 0.67; P < .001) vs ≥24 months (r = 0.32; P = 0.19). In subgroup analysis, breastfeeding for >24 months and high serum anti-SARS-CoV-2 RBD-S1 IgG levels predicted high HM IgG levels. This was an independent association in both linear and multiple regression models. Compared with breastfeeding <24 months, lactation >24 months was associated with increased HM anti-SARS-CoV-2 RBD-S1 levels.CommentsThis study in breastfeeding HCWs showed that the HM antibody levels were higher in women who had been breastfeeding for >24 months prior to receiving 2 doses of COVID-19 vaccine compared to participants who had been breastfeeding <24 months. Limitations include lack of in vitro plaque reduction neutralization tests which is the gold standard for evaluating SARS-CoV-2 antibody deactivation effectiveness. The study was conducted at a single site and did not assess infant serology or clinical outcome.According to the authors, breastfeeding by vaccinated women during a pandemic when young children are ineligible for vaccination may be encouraged. These results support findings from other studies of vaccines, such as influenza, in which the HM of vaccinated women may confer protection to their infants [3]. The benefits of maternal immunization, including the duration of protection afforded by HM from maternal recipients of mRNA COVID-19 vaccines, are research areas deserving of additional exploration. Additionally, further understanding of the association of the duration of receipt of HM from vaccinated women on infant immune responses would be beneficial in understanding the potential for passive protection through nutrition.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya.

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06-0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07-0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

Efficiency of transplacental transfer of respiratory syncytial virus (RSV) specific antibodies among pregnant women in Kenya

Background: Maternal immunisation to boost respiratory syncytial virus (RSV) antibodies in pregnant women, is a strategy being considered to enhance infant protection from severe RSV associated disease. However, little is known about the efficiency of transplacental transfer of RSV-specific antibodies in a setting with a high burden of malaria and HIV, to guide the implementation of such a vaccination program. Methods: Using a plaque reduction neutralization assay, we screened 400 pairs of cord and maternal serum specimens from pregnant women for RSV-specific antibodies. Participants were pregnant women of two surveillance cohorts: 200 participants from a hospital cohort in Kilifi, Coastal Kenya and 200 participants from a surveillance cohort in Siaya, Western Kenya. Transplacental transfer efficiency was determined by the cord to maternal titre ratio (CMTR). Logistic regression was used to determine independent predictors of impaired transplacental transfer of RSV-specific antibodies. Results: A total of 800 samples were screened from the 400 participants. At enrollment the median age was 25 years (Interquartile range (IQR): 21-31). Overall, transplacental transfer was efficient and did not differ between Kilifi and Siaya cohort (1.02 vs. 1.02; p=0.946) but was significantly reduced among HIV-infected mothers compared to HIV-uninfected mothers (mean CMTR: 0.98 vs 1.03; p=0.015). Prematurity <33 weeks gestation (Odds ratio [OR]: 0.23, 95% confidence interval [CI] 0.06–0.85; p=0.028), low birth weight <2.5 kgs (OR: 0.25, 95% CI: 0.07–0.94; p=0.041) and HIV infection (OR: 0.47, 95% CI:0.23-0.98; p=0.045) reduced efficiency of transplacental transfer among these women. Conclusions: Transplacental transfer of RSV-specific antibodies among pregnant women in Kenya is efficient. A consideration to integrate other preventive interventions with maternal RSV vaccination targeting infants born premature (<33 weeks gestation), with low birth weight <2.5 kgs, or HIV-infected mothers is likely to improve vaccine outcomes in this setting.

Yoga to improve maternal mental health and immune function during the COVID-19 crisis (Yoga-M2 trial): study protocol for a pilot randomized controlled trial.

Background: Mental health of women is adversely affected during pregnancy. A huge proportion of pregnant women suffer from stress and depression which negatively impacts birthweight and neuro-cognitive development of the fetus. The current crisis due to the COVID-19 pandemic further adds to the stressful situation. Yoga practiced during pregnancy has beneficial effects on improving stress and depression and preliminary evidence suggests that yoga-based interventions can improve immunity. This study aims to examine the feasibility, acceptability, and preliminary efficacy of a Yoga-based intervention for maternal Mental health and iMmunity (Yoga-M2) in a rural community in India. Methods: The study design will be a single-blind individual randomized parallel group-controlled pilot trial with 1:1 allocation ratio. Adult pregnant women, with gestational age between 12–24 weeks will be randomly allocated to either the Yoga-M2 group or the Enhanced Usual Care (EUC) group. Participants in the Yoga-M2 arm will attend weekly group yoga sessions for 12 weeks and will be encouraged to practice yoga at home. In the EUC arm, participants will receive a single session of health education. Eligibility of the participants, recruitment, retention-in-care, and study completion rates will be estimated and feasibility of delivering Yoga-M2 and acceptability of this intervention by the participants will be assessed. Change in the scores of the Perceived Stress Scale (PSS), EuroQoL 5 Dimensions Score (EQ-5D-5L), Wisconsin Upper Respiratory Symptom Severity Scale (WURSS-21), and serum C-Reactive Protein at three-months post-randomization will be used to assess preliminary efficacy. Discussion: The key outputs of this trial will be a structured intervention manual and evidence about the feasibility, acceptability, and preliminary efficacy of the intervention, establishing the foundation to undertake an explanatory randomized controlled trial to assess efficacy and cost-effectiveness of Yoga-M2 intervention. Trial registration: CTRI/2022/01/039701. Prospectively registered with the Clinical Trials Registry of India on 25 January 2022.

Seroprevalence against Diphtheria in Pregnant Women and Newborns in Colombia: New Arguments to Promote Maternal Immunization.

The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine is recommended during pregnancy for neonatal protection against pertussis, although little is known of the protection it provides against diphtheria. The work used a cross-sectional design to estimate seroprevalence against diphtheria in 805 pregnant women with ≥37 gestation weeks and their newborns whose deliveries were attended in eight hospitals randomly chosen from a subregion of Antioquia, Colombia and to explore factors related with maternal protection. Levels of IgG antibodies were determined by using a commercial enzyme-linked immunosorbent assay test. Placental transfer of antibodies and crude and adjusted prevalence ratio (aPR) were analyzed to describe factors related with maternal protection against diphtheria. Protection against diphtheria was observed in 91.7% (95% CI 90.3–93.0) of the pregnant women and 93.1% (95% CI 91.7–94.4) of newborns, whose antibody levels were positively correlated (Spearman’s r = 0.769; p = 0.000). Maternal protection could be influenced by having been vaccinated during the current pregnancy (aPR 0.85, 95% CI: 0.82–0.93). The protective effect of vaccination during pregnancy and the efficiency of maternal antibody transfers were detected. Public health efforts should focus on increasing Tdap vaccination during each pregnancy to protect mothers and newborns against diphtheria.

Cost-effectiveness of Respiratory Syncytial Virus Disease Prevention Strategies: Maternal Vaccine Versus Seasonal or Year-Round Monoclonal Antibody Program in Norwegian Children.

Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs. Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease. We estimate an annual average of 13517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb. Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.

Effectiveness of herb-partitioned moxibustion on the navel for pregnancy outcomes in patients with recurrent implantation failure undergoing in vitro fertilization and embryo transfer: a study protocol for a randomized controlled trial

BackgroundRecurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF.MethodsThis study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate.DiscussionIf the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice.Trial registrationChinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954. Registered on 8 July 2021.

Effects of Vertical Transmission of Respiratory Viruses to the Offspring.

Overt and subclinical maternal infections in pregnancy can have multiple and significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, the current concept of pregnancy as a state of systemic immunosuppression seems oversimplified and outdated. Undoubtedly, in pregnancy the maternal immune system undergoes complex changes to establish and maintain tolerance to the fetus while still protecting from pathogens. In addition to downregulated maternal immunity, hormonal changes, and mechanical adaptation (e.g., restricted lung expansion) make the pregnant woman more susceptible to respiratory pathogens, such as influenza virus, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Depending on the infectious agent and timing of the infection during gestation, fetal pathology can range from mild to severe, and even fatal. Influenza is associated with a higher risk of morbidity and mortality in pregnant women than in the general population, and, especially during the third trimester of pregnancy, mothers are at increased risk of hospitalization for acute cardiopulmonary illness, while their babies show higher risk of complications such as prematurity, respiratory and neurological illness, congenital anomalies, and admission to neonatal intensive care. RSV exposure in utero is associated with selective immune deficit, remodeling of cholinergic innervation in the developing respiratory tract, and abnormal airway smooth muscle contractility, which may predispose to postnatal airway inflammation and hyperreactivity, as well as development of chronic airway dysfunction in childhood. Although there is still limited evidence supporting the occurrence of vertical transmission of SARS-CoV-2, the high prevalence of prematurity among pregnant women infected by SARS-CoV-2 suggests this virus may alter immune responses at the maternal-fetal interface, affecting both the mother and her fetus. This review aims at summarizing the current evidence about the short- and long-term consequences of intrauterine exposure to influenza, RSV, and SARS-CoV-2 in terms of neonatal and pediatric outcomes.

Assessing Community Acceptance of Maternal Immunisation in Rural KwaZulu-Natal, South Africa: A Qualitative Investigation.

Despite the significant benefits of maternal immunisation, uptake remains low in many parts of the world. In this qualitative study, we aimed to assess the factors that influence pregnant women’s decision to engage with maternal immunisation in rural KwaZulu-Natal, South Africa. We conducted in-depth interviews with a total of 28 purposively sampled pregnant women and key informants using semi-structured topic guides. Data analysis was conducted using a modified Health Belief Model framework that included constructs of barriers to action, modifying factors of cue to action and perceived social norms. The findings show that traditional customs and institutional barriers such as low-quality health service delivery, long queues, and distance to the health facilities, immunisation vaccine stockouts and low levels of maternal knowledge influence the choice and decision to engage with maternal immunisation. Understanding health-related behaviours and addressing barriers to care is important in facilitating vaccination uptake. This study contributes to the understanding of maternal immunisation uptake in low-resource settings.