Maternal Influenza Immunization Research Articles

Potential Cost-Effectiveness of Maternal Influenza Immunisation in Low-Income Countries: An Explorative Modelling Study and Value of Information Analysis to Guide Future Clinical Research.

Maternal influenza immunisation (MII) is recommended for protecting pregnant women and infants under six months of age from severe disease related to influenza. However, few low-income countries have introduced this vaccine. Existing cost-effectiveness studies do not consider potential vaccine non-specific effects (NSE) observed in some settings, such as reductions in preterm birth. A decision tree model was built to examine the potential cost-effectiveness of MII in a hypothetical low-income country compared to no vaccination, considering possible values for NSE on preterm birth in addition to vaccine-specific effects on influenza. We synthesized epidemiological and cost data from low-income countries. All costs were adjusted to 2021 United States dollars (USD). We considered cost-effectiveness thresholds that reflect opportunity costs (USD 188 per disability-adjusted life year averted; range: USD 28-538). Results suggest that even a small (5%) NSE on preterm birth may make MII a cost-effective strategy in these settings. A value of information analysis indicated that acquiring more information on the presence and possible size of NSE of MII could greatly reduce the uncertainty in decision-making on MII. Further clinical research investigating NSE in low-income countries may be of high value to optimise immunisation policy.

Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes

Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization. To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns. Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021. Maternal BNT162b2 mRNA vaccination during pregnancy. Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status. The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks' gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72). This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

An evaluation of strategies to achieve greater than 90% coverage of maternal influenza and pertussis vaccines including an economic evaluation

BackgroundMaternal immunisation is an essential public health intervention aimed at improving the health outcomes for pregnant women and providing protection to the newborn. Despite international recommendations, safety and efficacy data for the intervention, and often a fully funded program, uptake of vaccines in pregnancy remain suboptimal. One possible explanation for this includes limited access to vaccination services at the point of antenatal care. The aim of this study is to evaluate the change in vaccine coverage among pregnant women following implementation of a modified model of delivery aimed at improving access at the point of antenatal care, including an economic evaluation.MethodsThis prospective multi-centre study, using action research design, across six maternity services in Victoria, Australia, evaluated the implementation of a co-designed vaccine delivery model (either a pharmacy led model, midwife led model or primary care led model) supported by provider education. The main outcome measure was influenza and pertussis vaccine uptake during pregnancy and the incremental cost of the new model (compared to existing models) and the cost-effectiveness of the new model at each participating health service.ResultsInfluenza vaccine coverage in 2019 increased between 50 and 196% from baseline. All services reduced their average cost per immunisation under the new platforms due to efficiencies achieved in the delivery of maternal immunisations. This cost saving ranged from $9 to $71.ConclusionOur study demonstrated that there is no ‘one size fits all’ model of vaccine delivery. Future successful strategies to improve maternal vaccine coverage at other maternity services should be site specific, multifaceted, targeted at the existing barriers to maternal vaccine uptake, and heavily involve local stakeholders in the design and implementation of these strategies. The cost-effectiveness analysis indicates that an increase in maternal influenza immunisation uptake can be achieved at a relatively modest cost through amendment of maternal immunisation platforms.

Disparities in maternal influenza immunization among women in rural and urban areas of the United States

Pregnant women and their infants are at high risk of influenza-associated complications. Although maternal immunization offers optimal protection for both, immunization rates remain low in the U.S. Women in rural communities may represent a difficult to reach group, yet immunization rates among rural-residing women have not been well evaluated. We analyzed data from the 2016–2018 Phase-8 Pregnancy Risk Assessment Monitoring System for 19 U.S. states, including 45,018 women who recently gave birth to a live infant. We compared the prevalence of influenza vaccination prior to or during pregnancy and receipt of a vaccine recommendation from a healthcare provider for rural vs. urban-residing women. We used average marginal predictions derived from multivariate logistic regression models to generate weighted adjusted prevalence ratios (aPR) and corresponding 95% CIs. Of the 45,018 respondents, 6575 resided in a rural area; 55.1% (95% CI: 53.3, 56.9) of rural-residing women and 61.3% (95% CI: 60.6, 61.9) of urban-residing women received an influenza vaccine prior to or during pregnancy. The prevalence of vaccination was 4% lower among rural-residing women (aPR: 0.96; 95% CI: 0.93, 0.99). The greatest difference in rural vs. urban immunization rates were observed for Hispanic women and women with no health insurance. Our results indicate that pregnant women residing in rural communities have lower rates of immunization. To prevent maternal and infant health disparities, it is important to better understand the barriers to maternal immunization along with efforts to overcome them.

The Power of First Impressions: Can Influenza Imprinting during Infancy Inform Vaccine Design?

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system, and lack of previous exposure to the virus is thought to synergistically play a role in the increased disease severity in younger age groups. No influenza vaccines are available for those under six months, although maternal influenza immunization is recommended. In children aged six months to two years, vaccine immunogenicity is dampened compared to older children and adults. Unlike older children and adults, the infant immune system has fewer antigen-presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. We contend that by understanding the influenza imprinting event in the context of the infant immune system, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune and respiratory development, current vaccine strategies, and highlights the importance of research into the imprinting event in infant animal models to develop more effective and protective vaccines for all including young children.

Assessment of indirect protection from maternal influenza immunization among non-vaccinated household family members in a randomized controlled trial in Sarlahi, Nepal

Influenza is a significant cause of morbidity and mortality worldwide, and the World Health Organization highly recommends maternal vaccination during pregnancy. The indirect effect of maternal vaccination on other close contacts other than newborns is unknown. To evaluate this, we conducted a nested substudy between 2011 and 2012 of influenza and acute respiratory illness (ARI) among household members of pregnant women enrolled in a randomized placebo-controlled trial of antenatal influenza vaccination in the rural district of Sarlahi, Nepal. Women were assigned to receive influenza vaccination or placebo during pregnancy and then they and their household members were followed up to 6 months postpartum with weekly symptom surveillance and nasal swab collection. Swabs were tested by RT-PCR for influenza. Rates of laboratory-confirmed influenza and of ARI were compared between vaccine and placebo groups using generalized estimating equations with a Poisson link function. Overall, 1752 individuals in 520 households were eligible for inclusion. There were 82 laboratory-confirmed influenza illness episodes, for a rate of 7.0 per 100 person-years overall. Of the influenza strains able to be typed, 29 were influenza A, 40 were influenza B, and 6 were coinfections with influenza A and B. The rate did not differ significantly whether the household was in the vaccine or placebo group (rate ratio (RR) 1.37, 95% confidence interval (CI) 0.83–2.26). The rate of ARI was 28.5 per 100 person-years overall and did not differ by household group (RR 0.99, 95% CI 0.72–1.36). Influenza vaccination of pregnant women did not provide indirect protection of unvaccinated household members.

Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials

SummaryBackgroundMaternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age.MethodsWe did a pooled analysis of three randomised controlled trials done in Nepal (2011–2014), Mali (2011–2014), and South Africa (2011–2013). Pregnant women, gestational age 17–34 weeks in Nepal, 28 weeks or more in Mali, and 20–36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190.Findings10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (–9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32–63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (–2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length.InterpretationThe assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations.FundingBill & Melinda Gates Foundation.

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

SummaryBackgroundSeasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018.MethodsWe estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries.FindingsIn 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries.InterpretationA large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries.FundingWHO; Bill & Melinda Gates Foundation.

Psychosocial determinants of pertussis and influenza vaccine uptake in pregnant women: A prospective study

ObjectiveTo identify the psychosocial factors influencing women’s uptake and willingness to receive pertussis and influenza vaccine during pregnancy. MethodsThe study population comprised 1364 healthy nulliparous pregnant women who participated in a prospective cohort study at two obstetric hospitals in South Australia between 2015 and 2017. Information on women's vaccination status, sociodemographic, lifestyle and psychological state were collected at 9–16 weeks’ gestation and medical case notes were checked post-delivery to verify the reported vaccination status. Poisson regression models were used to estimate the crude and adjusted prevalence ratios (aPRs) to identify psychosocial factors influencing uptake of vaccination during pregnancy. ResultsWillingness to receive the recommended maternal vaccines was high (90%). Overall, 79% and 48% received maternal pertussis and influenza vaccines respectively. There was no evidence to support the influence of psychosocial factors on women’s willingness to receive immunization during pregnancy. High levels of anxiety (aPR 0.98, 95% CI: 0.87–1.09) was not associated with uptake of maternal pertussis vaccine. However, elevated depressive symptoms (aPR 1.14, 95% CI: 1.00–1.30) and very high-perceived stress during pregnancy were significantly associated with receipt of pertussis vaccination (aPR 0.87; 95% CI 0.76–0.99). Women with mild depressive symptoms (aPR 1.21, 95% CI 1.00–1.44) and mild anxiety symptoms (aPR 1.21, 95% CI: 0.99–1.48) were more likely to receive influenza vaccine during pregnancy (aPR 1.27, 95% CI: 1.08–1.49). A history of major depressive disorder was independently associated with receipt of pertussis (aPR 1.16, 95% CI 1.06–1.26) and influenza vaccination during pregnancy (aPR 1.32; 95% CI 1.14–1.58). ConclusionRegardless of psychosocial factors, most women reported a positive willingness to receive the recommended vaccinations during pregnancy. However, psychosocial factors influenced the uptake of pertussis and influenza vaccines during pregnancy. Psychosocial factors should be taken into consideration in designing interventions and implementation of maternal pertussis and influenza immunization programs.

Risk of Respiratory Infection following Diarrhea among Adult Women and Infants in Nepal.

.Globally, diarrheal and respiratory infections are responsible for more than 24% of deaths in children aged less than 5 years. Historically, these disease entities have been studied separately; recent evidence suggests that preceding diarrheal disease may be a risk factor for subsequent respiratory illness. We used data from a community-based, prospective randomized trial of maternal influenza immunization of 3,693 pregnant women and their 3,646 infants conducted in rural Nepal from 2011 to 2014. A case-crossover design was used to determine whether the risk of respiratory infection in the 30 days following a diarrheal episode was increased compared with that 30 days prior. Diarrheal illness was a significant risk factor for subsequent respiratory illness in infants but not in women during pregnancy or in women up to six months postpartum. Diarrheal illness and respiratory infections remain important global sources of morbidity and mortality, and our study supports a causal relationship between them in infants.

Current Perspectives on Maternal Influenza Immunization

Pregnant women and young infants are more likely to experience severe complications associated with influenza infection and are at increased risk of hospitalization. Influenza vaccination during pregnancy produces antibodies which protect the mother against infection, and due to transplacental transfer of maternal antibodies before birth, it also protects the infant in the first few months of life. In many countries, influenza vaccination is recommended during pregnancy to protect mothers and their infants. In fact, influenza vaccine is the most widely used vaccine in pregnancy globally. When administered during pregnancy, the vaccine has been shown to be safe and effective for both mothers and their infants. Despite the health benefits, acceptance of influenza vaccine is low during pregnancy, indicating many women and infants are not protected against influenza. Concerted efforts are needed globally to improve the proportion of women and young infants who receive the health benefits of influenza vaccination.

2215. Diarrheal Illness as a Risk Factor for Subsequent Respiratory Infection Among Women and Infants in Nepal

BackgroundGlobally, diarrheal and respiratory infections are responsible for nearly one-quarter of deaths in children under 5 years old. Historically these diseases have been studied separately; recent evidence suggests that preceding diarrheal disease may be a risk factor for subsequent respiratory illness. We sought to identify whether diarrhea was associated with subsequent respiratory illness in adult women and infants in Nepal.MethodsWe used data from a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011 to 2014. Diarrhea episodes were defined as at least three self-reported watery bowel movements per day for one or more days. Respiratory illness episodes were defined as the presence of fever with an additional respiratory symptom. Diarrhea and respiratory illness episodes were identified through longitudinal household-based weekly symptom surveillance. A case-crossover design was used to determine whether risk of respiratory infection was increased in the 30 days following a diarrhea episode compared with the 30 days prior.ResultsOf 3,693 women in the study and their 3,646 infants, 525 (14.2%) women experienced one or more episodes of diarrhea during pregnancy, 226 (9.4%) women experienced one or more episodes of diarrhea after pregnancy, and 342 (9.4%) infants had one or more episodes of diarrhea. The incidence of respiratory episodes during the exposure and control periods was approximately 2–5% in adults and 8–10% in infants. Preceding diarrhea was not significantly associated with respiratory infection in adult women or infants. There was a slight trend toward greater incidence of diarrhea during the exposure period among infants (Figure 1), but it was not statistically significant. These results held after a sensitivity analysis limiting follow-up time to 15 days before and after diarrhea episode.ConclusionIn this study of pregnant and postpartum women and their infants in Nepal, diarrheal illness was not a significant risk factor for subsequent respiratory illness. Disclosures All authors: No reported disclosures.

Phylogenetic characterization of rhinoviruses from infants in Sarlahi, Nepal.

ProblemRhinoviruses (RVs), the most common causes of acute respiratory infections in young children and infants, are highly diverse genetically.ObjectiveTo characterize the RV types detected with respiratory illness episodes in infants in Nepal.Study methodsInfants born to women enrolled in a randomized trial of maternal influenza immunization in rural, southern Nepal were followed with household‐based weekly surveillance until 180 days of age. Infants with respiratory symptoms had nasal swabs tested for twelve respiratory viruses. A subset with RV alone was selected for sequencing of the VP4/2 gene to identify RV types.ResultsAmong 547 RV‐only positive illnesses detected from December 2012 to April 2014, 285 samples (52%) were sequenced. RV‐A, B, and C species were detected in 193 (68%), 18 (6%), and 74 (26%) specimens, respectively. A total of 94 unique types were identified from the sequenced samples, including 52 RV‐A, 11 RV‐B, and 31 RV‐C. Multiple species and types circulated simultaneously throughout the study period. No seasonality was observed. The median ages at illness onset were 88, 104, and 88 days for RV‐A, B, and C, respectively. The median polymerase chain reaction cycle threshold values did not differ between RV species. No differences between RV species were observed for reported respiratory symptoms, including pneumonia, or for medical care‐seeking.ConclusionsAmong very young, symptomatic infants in rural Nepal, all three species and many types of RV were identified; RV‐A was detected most frequently. There was no association between RV species and disease severity.

Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes

IntroductionThe purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data. Materials and methodsA double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine was conducted in South Africa from March 2011 until after the 2012 influenza season when the infants born had reached the age of 24 weeks. Mothers were administered the vaccine or placebo during pregnancy at a gestation of 20 to 36 weeks. A comparison of rates of fetal death, low birth weight, small for gestational age birth, and preterm birth, between vaccinated and placebo groups was made. Fetal outcome differences between the groups were measured using Student’s t-tests, vaccine efficacy with 95% confidence intervals, and Poisson regression for incidence rates. All analyses except fetal death excluded mothers who were administered vaccine or placebo after 34 weeks gestational age. ResultsThere were 2116 HIV-uninfected pregnant women age 18 to 38 years in the trial; 2005 infants were born to mothers where vaccine or placebo had been administered ≥ 14 days prior to delivery, and there were 6 miscarriages and 23 stillbirths. There was no significant vaccine efficacy (with [95% confidence interval]) on fetal death (−21.2% [−150.8, 41.4]), low birth weight (−11.1% [−42.3, 12.5]), small for gestational age birth (−9.9% [−35.6, 11.0]), or preterm birth (−21.3% [−60.5, 8.3]). Neither was vaccine efficacy demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (1832 outcomes available). ConclusionWe did not find a beneficial effect of trivalent inactivated influenza vaccine during pregnancy on adverse fetal outcomes.

Infant Pneumococcal Carriage During Influenza, RSV, and hMPV Respiratory Illness Within a Maternal Influenza Immunization Trial.

In this post-hoc analysis of midnasal pneumococcal carriage in a community-based, randomized prenatal influenza vaccination trial in Nepal with weekly infant respiratory illness surveillance, 457 of 605 (75.5%) infants with influenza, respiratory syncytial virus (RSV), or human metapneumovirus (hMPV) illness had pneumococcus detected. Pneumococcal carriage did not impact rates of lower respiratory tract disease for these 3 viruses. Influenza-positive infants born to mothers given influenza vaccine had lower pneumococcal carriage rates compared to influenza-positive infants born to mothers receiving placebo (58.1% versus 71.6%, P = 0.03). Maternal influenza immunization may impact infant acquisition of pneumococcus during influenza infection. Clinical Trials Registration. NCT01034254.

The under appreciated need for maternal and newborn immunization: call to action

In spite of clear evidence regarding the safety and efficacy of maternal and neonatal immunization, the accetance of maternal influenza and pertussis immunization and neonatal Hepatitis B vaccination has been disappointingly slow to reach optimal levels in the United States. Maternal influenza disease is associated with increased birth defects, premature delivery, and the delivery of small for gestational age infants. Influenza immunization has been recommended for all women who are or will be pregnant, regardless of trimester, during influenza season (October through May), but only about half receive them. Concerns about influenza immunization clearly overlook the solid data regarding the overall association between influenza immunization and decreased mortality and morbidity for both mothers and infants. Pertissis disease in infants under 2 months of age is associated with significantly increased morbidity and mortality. Pertussis incidence in the US has seen a significant increase in the past two decades in most age groups including that of parents and siblings. Recommended attempts to decrease infant pertussis infection include both maternal immunization and immunization of individuals who are expected to come in contact with these newborn infants (cocooning). Transmission of maternal Hepatitis B infection to their infants is associated with a significant incidence of chronic disease with subsequent cirrhosis and death. The administration of both Hepatitis B immune globulin and a “birth dose” of Hepatitis B vaccine have been demonstrated to be very safe and effective in preventing infant acquisition of Hepatitis B infection from infected mothers. A birth dose of Hepatitis B vaccine should be administered to every newborn.

Effect of Diarrheal Illness During Pregnancy on Adverse Birth Outcomes in Nepal.

BackgroundAdverse birth outcomes, including low birthweight, small for gestational age (SGA), and preterm birth, contribute to 60%–80% of infant mortality worldwide. Little published data exist on the association between diarrhea during pregnancy and adverse birth outcomes.MethodsData were used from 2 community-based, prospective randomized trials of maternal influenza immunization during pregnancy conducted in rural Nepal from 2011 to 2014. Diarrheal illnesses were identified through longitudinal household-based weekly symptom surveillance. Diarrhea episodes were defined as at least 3 watery bowel movements per day for 1 or more days with 7 diarrhea-free days between episodes. The Poisson and log-binomial regression were performed to evaluate baseline characteristics and association between diarrhea during pregnancy and adverse birth outcomes.ResultsA total of 527 of 3693 women in the study (14.3%) experienced diarrhea during pregnancy. Women with diarrhea had a median of 1 episode of diarrhea (interquartile range [IQR], 1–2 episodes) and 2 cumulative days of diarrhea (IQR, 1–3 days). Of women with diarrhea, 85 (16.1%) sought medical care. In crude and adjusted analyses, women with diarrhea during pregnancy were more likely to have SGA infants (42.6% vs 36.8%; adjusted risk ratio = 1.20; 95% confidence interval, 1.06–1.36; P = .005). Birthweight and preterm birth incidence did not substantially differ between women with diarrhea during pregnancy and those without.ConclusionsDiarrheal illness during pregnancy was associated with a higher risk of SGA infants in this rural South Asian population. Interventions to reduce the burden of diarrheal illness during pregnancy may have an impact on SGA births in resource-limited settings.

The impact of timing of maternal influenza immunization on infant antibody levels at birth

Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunization is a potent tool to protect both these at-risk groups. While the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunized in the second trimester of pregnancy had the highest antibody titres compared to children immunized in the third trimester. The aim of the current study was to investigate how the timing of maternal influenza immunization impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both immunoglobulin (Ig)G-binding enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunization was performed less than 4weeks before birth. These studies confirm that immunization during pregnancy increases the antibody titre in infants. Importantly, antibody levels in cord blood were significantly higher when the mother was vaccinated in either trimesters 2 or 3, although titres were significantly lower if the mother was immunized less than 4weeks before birth. Based on these data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available.

2278. Maternal Immunization Rates With Tetanus–Diphtheria–Acellular Pertussis and Influenza Vaccines in the United States: A Retrospective Claims Database Analysis

BackgroundThe Advisory Committee on Immunization Practices (ACIP) recommends maternal immunization (MI) with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during every pregnancy, preferably between 27–36 weeks of gestation, as well as influenza vaccination for all women who are pregnant or who might be pregnant in the influenza season.MethodsThis retrospective cohort analysis characterizes the rate of Tdap and influenza vaccination among large national samples of pregnant women in the United States using administrative claims data. The MarketScan® Commercial Claims and Encounters (“Commercial”) and the Multi-State Medicaid Databases (“Medicaid”) were used to identify pregnancies between January 1, 2010 and April 30, 2017. Diagnosis and procedure codes that describe gestational age at pregnancy end were used to estimate the date of last menstrual period (LMP) or the index date (Figure 1). Eligible pregnancies had ≥6 months of continuous enrollment prior to index date (“baseline”) through 60 days after pregnancy end (“follow-up”). Maternal Tdap and influenza immunization rates are described by calendar year of pregnancy end. Analyses are reported separately for Commercial and Medicaid cohorts.ResultsA total of 1,862,705 and 628,079 eligible pregnancies in the Commercial and Medicaid databases, respectively, were identified. After the 2013 ACIP recommendation to administer Tdap vaccination during each pregnancy, the proportion of pregnancies vaccinated against Tdap was 39% in 2014 and increased to 54% in 2016 for the Commercial cohort (Figure 2). A similar trend for Tdap MI was observed for the Medicaid cohort (Figure 3). In 2016, 41% and 25% of all pregnancies received influenza vaccination in the Commercial and Medicaid cohorts, respectively. Tdap and influenza MI rates also varied by several factors, including maternal age group, geographic region, urban/rural location, and race/ethnicity. ConclusionIn this analysis of large claims databases, for pregnancies ending in 2016 in the Commercial cohort, over 50% received Tdap vaccination and over 40% received influenza vaccination, whereas, in the Medicaid cohort, 30% of all pregnancies were vaccinated against Tdap and 25% received influenza vaccination.Disclosures P. Ghaswalla, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary. J. E. Poirrier, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary. E. Packnett, GSK: Research Contractor, Research support. D. Irwin, GSK: Research Contractor, Research support. S. Gray, GSK: Research Contractor, Research support. P. Buck, GSK: Employee and Shareholder, GSK stock options or restricted shares and Salary.

1096. Effect of Diarrheal Illness During Pregnancy on Adverse Birth Outcomes in Nepal

BackgroundAdverse birth outcomes, including low birthweight (LBW), small-for-gestational-age (SGA) and preterm birth, contribute to 60–80% of infant mortality worldwide. Little published data exist on the association between diarrhea during pregnancy and adverse birth outcomes. We sought to identify whether diarrhea during pregnancy was associated with adverse birth outcomes.MethodsWe used data from a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011 to 2014. Illness episodes were defined as at least three watery bowel movements per day for one or more days with 7 diarrhea-free days between episodes. Diarrheal illnesses were identified through longitudinal household-based weekly symptom surveillance. The c2 test, two-sample t-test, and log-binomial regression were performed to evaluate baseline characteristics and the association between diarrhea during pregnancy and adverse birth outcomes.ResultsOf 3,682 women in the study, 527 (14.3%) experienced one or more episodes of diarrhea during pregnancy. Diarrhea incidence was not seasonal. Women with diarrhea had a median of one episode of diarrhea (interquartile range (IQR) 1–2 episodes) and two cumulative days of diarrhea (IQR 1–3 days). Of women with diarrhea, 16.1% (85) sought medical care. Mean maternal age, parity, biomass cook stove use, home latrine, water source, caste, and smoking did not differ in pregnant women with and without diarrhea. In crude and adjusted analyses, women with diarrhea during pregnancy were significantly more likely to have SGA infants (42.6% vs. 36.8%; adjusted risk ratio=1.20, 95% CI 1.06–1.36, P = 0.005). LBW and preterm birth incidence did not significantly differ between women with diarrhea during pregnancy and those without. There was no significant association between seeking medical care for diarrhea and birth outcomes. ConclusionDiarrheal illness during pregnancy was associated with a significantly higher risk of SGA infants in this rural South Asian population. Interventions to reduce the burden of diarrheal illness during pregnancy may have an impact on SGA births in resource-limited settings.Disclosures All authors: No reported disclosures.