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This is a Brighton Collaboration Case Definition of the term ‘‘Multisystem Inflammatory Syndrome in Children and Adults (MIS-C/A)” to be utilized in the evaluation of adverse events following immunization. The case definition was developed by topic experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2. The format of the Brighton Collaboration was followed, including an exhaustive review of the literature, to develop a consensus definition and defined levels of certainty. The document underwent peer review by the Brighton Collaboration Network and by selected expert external reviewers prior to submission. The comments of the reviewers were taken into consideration and edits incorporated into this final manuscript. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND.

BACKGROUND: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings.METHODS: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated.RESULTS: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs.CONCLUSIONS: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.

Background Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the coronavirus disease 2019 (COVID-19) pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. Methods Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. Results From 14 December 2020 to 30 April 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21–66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11–78 days) before MIS-A onset. All 20 patients had laboratory evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6–45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. Conclusions Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring., Seven of 20 MIS-A patients received COVID-19 vaccination before illness onset. All patients had evidence of prior SARS-CoV-2 infection. Given widespread COVID-19 vaccinations in the United States, the lack of reporting of MIS-A associated with vaccination alone is reassuring.

Background: Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen’s superior safety and adherence. Methods: We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving this regimen between 2017 and 2019. Frequencies of selected outcomes were compared to data collected in a literature review. Results: In this retrospective chart review, pediatric patients ages 2 to 20 years receiving 3HP with DOT for latent tuberculosis experienced higher adverse event rates, more severe adverse events, and higher treatment discontinuation than that which has been previously reported in the literature. A possible explanation for this finding is that our cohort’s race/ethnicity differed from the cohorts used in the literature. Conclusions: Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the regimen’s safety and tolerability.

Millions of children travel annually, whether they are refugees, international adoptees, visitors, or vacationers. Although most young travelers do well, many develop a febrile illness during or shortly after their trips. Approaching a fever in the returning traveler requires an appropriate index of suspicion to diagnose and treat in a timely manner. As many as 34% of patients with recent travel history are diagnosed with routine infections, but serious infections such as malaria, enteric fever, and dengue fever should be on the differential diagnosis due the high morbidity and mortality in children.

Background: Pregnant women have an elevated risk of illness and hospitalisation from influenza. Pregnant women are recommended to be prioritised for influenza vaccination during any stage of pregnancy. The risk of seasonal influenza varies substantially throughout the year in temperate climates; however, there is limited knowledge of how vaccination timing during pregnancy impacts the benefits received by the mother and foetus. Objectives: To compare antenatal vaccination timing with regard to influenza vaccine immunogenicity during pregnancy and transplacental transfer to their newborns. Methods: Studies were eligible for inclusion if immunogenicity to influenza vaccine was evaluated in women stratified by trimester of pregnancy. Haemagglutination inhibition (HI) titres, stratified by trimester of vaccination, had to be measured at either pre-vaccination and within one month post-vaccination, post-vaccination and at delivery in the mother, or in cord/newborn blood. Authors searched PubMed, Scopus, Web of Science and EMBASE databases from inception until June 2016 and authors of identified studies were contacted for additional data. Extracted data were tabulated and summarised via random-effect meta-analyses and qualitative methods. Results: Sixteen studies met the inclusion criteria. Meta-analyses found that compared with women vaccinated in an earlier trimester, those vaccinated in a later trimester had a greater fold increase in HI titres (1.33- to 1.96-fold) and higher HI titres in cord/newborn blood (1.21- to 1.64-fold). Conclusions: This review provides comparative analysis of the effect of vaccination timing on maternal immunogenicity and protection of the infant that is informative and relevant to current vaccine scheduling for pregnant women.

Background Acute gastroenteritis (AGE) and acute respiratory infections (ARIs) cause significant pediatric morbidity and mortality. Developing childhood vaccines against major enteric and respiratory pathogens should be guided by the natural history of infection and acquired immunity. The United States currently lacks contemporary birth cohort data to guide vaccine development. Objective The PREVAIL (Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal) Cohort study was undertaken to define the natural history of infection and immune response to major pathogens causing AGE and ARI in US children. Methods Mothers in Cincinnati, Ohio, were enrolled in their third trimester of pregnancy, with intensive child follow-up to 2 years. Blood samples were obtained from children at birth (cord), 6 weeks, and 6, 12, 18, and 24 months. Whole stool specimens and midturbinate nasal swabs were collected weekly and tested by multipathogen molecular assays. Saliva, meconium, maternal blood, and milk samples were also collected. AGE (≥3 loose or watery stools or ≥1 vomiting episode within 24 hours) and ARI (cough or fever) cases were documented by weekly cell phone surveys to mothers via automated SMS text messaging and review of medical records. Immunization records were obtained from registries and providers. follow-up ended in October 2020. Pathogen-specific infections are defined by a PCR-positive sample or rise in serum antibody. Results Of the 245 enrolled mother–child pairs, 51.8% (n=127) were White, 43.3% (n=106) Black, 55.9% (n=137) publicly insured, and 86.5% (n=212) initiated breastfeeding. Blood collection was 100.0% for mothers (n=245) and 85.7% for umbilical cord (n=210). A total of 194/245 (79.2%) mother–child pairs were compliant based on participation in at least 70% (≥71/102 study weeks) of child-weeks and providing 70% or more of weekly samples during that time, or blood samples at 18 or 24 months. Compliant participants (n=194) had 71.0% median nasal swab collection (IQR 30.0%-90.5%), with 98.5% (191/194) providing either an 18- or 24-month blood sample; median response to weekly SMS text message surveys was 95.1% (IQR 76.5%-100%). Compliant mothers reported 2.0 AGE and 4.5 ARI cases per child-year, of which 25.5% (160/627) and 38.06% (486/1277) of cases, respectively, were medically attended; 0.5% of AGE (3/627) and 0.55% of ARI (7/1277) cases were hospitalized. Conclusions The PREVAIL Cohort demonstrates intensive follow-up to document the natural history of enteric and respiratory infections and immunity in children 0-2 years of age in the United States and will contribute unique data to guide vaccine recommendations. Testing for pathogens and antibodies is ongoing. International Registered Report Identifier (IRRID) RR1-10.2196/22222

Importance Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference −2.7%; 95% CI, −5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study’s results support using either vaccine to prevent influenza in older adults. Trial Registration ClinicalTrials.gov Identifier:NCT03183908

Background The ACIP recommends influenza and Tdap vaccination during pregnancy to reduce the risk of influenza and pertussis in the mother and her infant. We assessed influenza and Tdap vaccination coverage and associated factors among pregnant women enrolled in PREVAIL, a prospective birth cohort study in Cincinnati, OH. We assessed sensitivity and specificity of self report for both vaccines against state registry, maternal healthcare provider, and work-place records. Methods We enrolled and interviewed 265 pregnant women regarding self-reported receipt of influenza and Tdap vaccines, and obtained vaccine records from registry, electronic medical record, provider, employer, or pharmacy. We grouped subjects by documented vaccination status and analyzed demographic variables and vaccine attitudes regarding efficacy, safety, and hesitancy using unadjusted Fisher exact tests. We analyzed sensitivity and specificity of maternal recall. Results We identified documentation of influenza and Tdap vaccine receipt during pregnancy in 172/265 (64.9%) and 238/265 (89.8%) of women, respectively (Figure 1); by self report, 177/265 (66.8%) reported receiving influenza and 221/265 (83.4%) Tdap vaccine. The two most common primary reasons cited for receiving influenza vaccine were “to protect my baby” (36.7%) and “to protect myself” (26%; Figure 2). Pregnant women were more likely to get Tdap vaccine if a healthcare worker recommended it (OR 5.4). Subjects were more likely to get influenza vaccine if they believed it was effective in preventing influenza in themselves (OR 9.0) or their babies (OR 8.1). While positive recall had a high concordance (95.2% and 93.4% for influenza and Tdap, respectively), 12.5% and 32.1% of mothers incorrectly recalled not receiving an influenza or Tdap vaccine, respectively, that was documented as received in the records (Figure 3). Conclusion We found high concordance between maternal recall and verification for both influenza and Tdap vaccines. In this single-site cohort of 265 women, self report was a reliable measure of vaccination status among pregnant women. Provider communication to pregnant women regarding effectiveness of influenza and Tdap vaccinations for themselves and their infants may lead to higher maternal vaccination rates. Disclosures All authors: No reported disclosures.

Background Influenza vaccination has been shown to reduce influenza risk in pregnant women and their infants who are not yet age-eligible for vaccine. Ascertainment of vaccination history is important for vaccine safety and effectiveness evaluations. Our goals were to (a) determine coverage, location, and timing of maternal influenza vaccination and (b) compare a subset of self-reported influenza vaccinations with documented vaccine records. Methods We enrolled children < 18 years. with acute respiratory illness in 7 pediatric hospitals and emergency departments in the New Vaccine Surveillance Network from December 1, 2016 to October 31, 2018. We interviewed all mothers of enrolled infants < 1 year, and obtained mother’s influenza vaccine information while pregnant. As an option, sites obtained maternal influenza vaccine records from reported sources (e.g., registries, provider records, pharmacies). Results Among 5,458 mothers, 2,944 (54%) self-reported receiving influenza vaccine during pregnancy (57% in 2016–2017; 51% in 2017–2018), varying from 49% to 74% by site. Among self-reported vaccinees, 17%, 36%, and 47% received vaccine during their first, second, and third trimester, respectively. Most women (76%) were vaccinated at their OB/GYN or midwife office, 7% at their primary care provider, 7% at their workplace, and 5% at a retail pharmacy. Among 1,338 infants < 6 months. during early influenza season (i.e., born from June to August) and thus ineligible for vaccination, only 46% of mothers reported receiving vaccine during pregnancy (42% reported not receiving it, 12% were unsure). Of 2,242 women for whom vaccine verification was attempted, 1,491 (67%) self-reported receiving influenza vaccine during pregnancy; of those, documentation of vaccine receipt was found for 901 (60%). Conclusion Influenza vaccination coverage among pregnant women was suboptimal, potentially increasing the risk of influenza in unvaccinated pregnant women. Infants born to unvaccinated women, particularly those born from June to August, may also be at higher risk since they are not age-eligible to receive vaccine before influenza season. The optimal approach to ascertainment of maternal vaccination history with accuracy and completeness merits further investigation. Disclosures All authors: No reported disclosures.

Background Respiratory viruses are associated with most asthma exacerbations (AEx) in children; however, the role of different viruses in AEx is unclear. We describe respiratory virus detections among pediatric inpatients with AEx (AEx-inpatients). Methods Through active, prospective surveillance at 7 US medical centers, we enrolled inpatients ( Results We tested 3,897 inpatients with ARI; of whom, 954 were AEx-inpatients. Most AEx-inpatients (741/954 [78%]) reported an asthma/RAD history. Viruses were more frequently detected among AEx-inpatients Conclusion AEx-inpatients Disclosures All authors: No reported disclosures.

The intranasal live attenuated influenza vaccine (LAIV), FluMist, has been widely appreciated by pediatricians, parents, and children alike for its ease of administration. However, concerns regarding lack of effectiveness in recent influenza seasons led to the CDC Advisory Committee on Immunization Practices (ACIP) recommendation to administer inactivated influenza vaccines (IIVs), and not LAIV, during the 2016–17 and 2017–18 seasons. Given that data from previous years demonstrated equivalent and even improved efficacy of LAIV compared with IIV, these recent data were surprising, raising many questions about the potential mechanisms underlying this change. This review seeks to summarize the history of LAIV studies and ACIP recommendations with a focus on the recent decrease in vaccine effectiveness (VE) and discordant results among studies performed in different countries. Decreased VE for A/H1N1pdm09 viruses represents the most consistent finding across studies, as VE has been low every season these viruses predominated since 2010–11. Potential explanations underlying diminished effectiveness include the hypothesis that prior vaccination, reduced thermostability of A/H1N1pdm09, addition of a fourth virus, or reduced replication fitness of A/H1N1pdm09 strains may have contributed to this phenomenon. Ongoing studies and potential alterations to LAIV formulations provide hope for a return of effective LAIV in future influenza seasons.

We invite readers to contribute case presentations and discussions. Please use the Submit and Track My Manuscript link on the Pediatrics in Review homepage: http://pedsinreview.aappublications.org. A previously healthy 4-year-old boy presents for evaluation of a unilateral nose bleed refractory to compression lasting for 1.5 hours. He has had episodes of epistaxis in the past secondary to nasal manipulation but none this severe. Three weeks ago he had a runny nose and congestion, which are now resolved. His family denies vision changes, headaches, nausea, hematuria, dysuria, any known ingestions, or any skin flushing. There is no history of bleeding disorders in his family. On physical examination he is afebrile, with a heart rate of 121 beats per minute, a respiratory rate of 24 breaths per minute, a right arm blood pressure of 200/130 mm Hg, and an oxygen saturation of 99% on room air. His weight is 17 kg (50th percentile) and height is 112 cm (95th percentile). He appears well and has normal physical examination findings, with the exception of an abdominal bruit and barely palpable femoral pulses. Initial laboratory results are as follows: white blood cell count, 21,900/μL (21.9 × 109/L); absolute neutrophil count, 18,400/μL (18.4 × 109/L); absolute lymphocyte count, 2100/μL (2.1 × 109/L); hemoglobin, 9.9 g/dL (99 g/L); platelet count, 324 × 103/μL (324 × 109/L); mean corpuscular volume, 85 fL; red blood cell distribution width, 13.5%; an unremarkable peripheral blood smear; urea nitrogen, 45 mg/dL (16.1 mmol/L); creatinine, 1.39 mg/dL (123 μmol/L); and normal serum electrolyte levels. The results of thyroid function studies, coagulation profile, and urinalysis are normal. Renal ultrasonography with Doppler and head computed tomography results are interpreted as normal. Electrocardiography suggests left ventricular hypertrophy, and echocardiography reveals left ventricular hypertrophy. An additional …

Bartonella henselae commonly involves the mononuclear phagocyte system (MPS), and its most common presentation is lymphadenitis. Rarely, it can cause isolated osteomyelitis. We present a case of a 3 year old with constitutional symptoms and new onset of limp. Previously reported cases of osteomyelitis due to B. henselae are also reviewed here, keeping the index case in mind.We conducted a Medline search using MeSH subject headings Bartonella and osteomyelitis, limited to humans.The index case is a 3-year-old female who had a subacute presentation with new-onset leg pain and fever. Subsequent imaging demonstrated osteomyelitis of the acetabulum. Multiple diagnostic attempts were unsuccessful, and the patient did not respond to empiric therapy. Despite indeterminate serology, the diagnosis of Bartonella osteomyelitis was eventually confirmed by PCR on bone biopsy of the lesion. The literature search revealed 48 publications, which were reduced to 28 when limiting articles to the English language and the pediatric population. After a report of 36 pediatric cases in 2007, there have been an additional 12 pediatric cases since 1998. Generally, these patients had a subacute presentation with relatively mild constitutional symptoms. Most commonly, bone involvement occurred as osteolytic lesions of the axial skeleton. Of the total 48 cases reported, only four reported involvement of the axial skeleton.We present the first case, to our knowledge, of pediatric osteomyelitis of the pelvis due to B. henselae with indeterminate serologic and positive PCR results. Bartonella osteomyelitis should be included in the differential diagnosis when typical pathogens are not identified or if the patient is slow to respond to standard therapies. The sensitivity of tissue PCR for Bartonella osteomyelitis is now better than the current gold standard of serology, and new management guidelines may need to reflect this.

Background Vaccines are highly effective at preventing infectious diseases in children, and prevention is especially important in resource-limited countries where treatment is difficult to access. In Honduras, the World Health Organization (WHO) reports very high immunization rates in children. To determine whether or not these estimates accurately depict the immunization coverage in non-urban regions of the country, we compared the WHO data to immunization rates obtained from a local database tool and community health center records in rural Intibucá, Honduras. Methods We used data from two sources to comprehensively evaluate immunization rates in the area: 1) census data from a local database and 2) immunization data collected at health centers. We compared these rates using logistic regression, and we compared them to publicly available WHO-reported estimates using confidence interval inclusion. Results We found that mean immunization rates for each vaccine were high (range 84.4 to 98.8 percent), but rates recorded at the health centers were significantly higher than those reported from the census data (p≤0.001). Combining the results from both databases, the mean rates of four out of five vaccines were less than WHO-reported rates (p p=0.03). The rates by individual vaccine were similar across townships (p >0.05), except for diphtheria/tetanus/pertussis vaccine (p=0.02) and oral polio vaccine (p Conclusions Immunization rates in Honduras were high across data sources, though most of the rates recorded in rural Honduras were less than WHO-reported rates. Despite geographical difficulties and barriers to access, the local database and Honduran community health workers have developed a thorough system for ensuring that children receive their immunizations on time. The successful integration of community health workers and a database within the Honduran decentralized health system may serve as a model for other immunization programs in resource-limited countries where health care is less accessible.

BACKGROUND Limited data are available in Honduras that describe the etiology and seasonality of respiratory infections, especially in rural outpatient settings. Better data may lead to improved therapeutic and preventive strategies. The goal of our study was to determine the viral etiology and seasonality of acute respiratory infections in a rural Honduran population of children. METHODS Prospective clinic surveillance was conducted to identify children < 5 years of age presenting with respiratory symptoms of < 5 days duration. We obtained data on age, sex, medical history, breastfeeding history, symptoms, risk factors, household setting, temperature, respiratory rate and chest examination findings. To assess the association between specific viruses and weather, regional meteorological data were collected. Nasopharyngeal samples were tested for 16 respiratory viruses using a multiplex polymerase chain reaction panel. RESULTS From February 2010 through June 2011, 345 children < 5 years of age were enrolled; 17%, 23%, 30% and 31% were

PURPOSE OF REVIEW: This review highlights recent progress toward understanding complex interactions between diarrhea pneumonia and undernutrition among children in low-income and middle-income countries. RECENT FINDINGS: New studies parallel earlier reports that diarrhea and pneumonia impair childrens growth and that underlying malnutrition is a major risk factor for these conditions. Episodes of diarrhea may predispose to pneumonia in undernourished children. Additional studies support breastfeeding and micronutrient supplementation for the prevention and control of diarrhea and pneumonia. Malnutrition may partially account for the reduced efficacy of oral rotavirus vaccines in low-income countries. Immunization of pregnant women against influenza also appears to reduce intrauterine growth retardation. Immunization of infants against Streptococcus pneumoniae may improve their growth. New genetic studies indicate that polymorphisms in apolipoprotein E or the leptin receptor modulate childrens risk for diarrhea and Entamoeba histolytica infection respectively thereby linking two genes important for lipid metabolism to enteric infections. SUMMARY: Significant advances have been made in understanding the vicious cycle of malnutrition diarrhea and pneumonia in developing countries. Future challenges will be to translate this progress into effective and widely accessible public health measures.

Although pediatricians are well aware that influenza can be a problem for infants younger than 6 months, they may be less familiar with the high rates of influenza disease and complications among pregnant women. We provide here a summary of recent data on increased risk of influenza in pregnancy and in very young infants and on vaccine protection of these 2 groups at high-risk. Pediatricians should be aware of their central role in assisting in the vaccine prevention of influenza in pregnancy and in the young infant. Healthy pregnant women are at increased risk of morbidity and mortality from pandemic influenza infection. During the 1918–1919 influenza pandemic, the case-fatality rate of pregnant women with influenza was reported to be 30% to 50% in the United States.1,–,3 Similarly, the 2009 H1N1 influenza pandemic disproportionately affected pregnant women.4,–,6 By August 2009, 788 H1N1-infected pregnant women had been reported to the Centers for Disease Control and Prevention (CDC), and 30 of these women died (5% of all reported 2009 H1N1 influenza deaths in this period).7 The increased risk of influenza during pregnancy is related to the physiologic changes of decreased pulmonary tidal volume and increased cardiac output. In addition, suppressed type 1 T-helper cell-mediated immunity impairs maternal response to infection with several viruses including influenza and smallpox.8,9 Seasonal influenza-related hospitalization in healthy pregnant women occurs at a rate of 1 to 2 per 1000,10,–,12 a risk that is 18-fold greater than that for healthy nonpregnant women.10 Historically, young infants have had high rates … Address correspondence to Mark C. Steinhoff, MD, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, ML-2048, Cincinnati, OH 45229-3039. E-mail: mark.steinhoff{at}cchmc.org