Effect of maternal vaccination on infant morbidity in Bangladesh.

BACKGROUND: Risk factors of infant mortality in Africa and south Asian countries have been broadly discussed. However, infant morbidity is largely underestimated. We analyzed the data from a randomized vaccine trial in Bangladesh to identify and assess the effect of risk factors on infant morbidity. METHODS: Pregnant women were randomly assigned to receive either inactivated influenza vaccine or pneumococcal polysaccharide vaccine and the infants were randomly assigned to receive 7-valent pneumococcal conjugate vaccine or Hib conjugate vaccine at week 6, 10 and 14. The data were collected from August 2004 through December 2005. Each pair of infant and mother were followed for 24 weeks after birth with weekly visits. Generalized estimating equations (GEE) for repeated measurements and Poisson regression models were used to identify the risk factors and evaluate their effect on the longitudinal incidence and total number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem and pneumonia. RESULTS: A total of 340 pregnant women were randomized with mean age of 25 years. The baseline mother and infant characteristics were similar between two treatment groups. Exclusive breastfeeding and higher paternal education level were common factors associated with lower infant morbidity of RIF (adjusted OR = 0.40 and 0.94 with p < 0.01 and p = 0.02, respectively), diarrhea disease (adjusted OR = 0.39 and 0.95 with p < 0.01 and p = 0.04, respectively), and ear problem (adjusted OR = 0.20 and 0.76 with p < 0.01 and p < 0.01, respectively). Maternal influenza vaccine significantly reduced the incidence of RIF (adjusted OR = 0.54; p < 0.01) but not diarrhea disease or ear problem (p > 0.05). Female infants had lower incidence of diarrhea disease (adjusted OR = 0.67; p = 0.01) and ear problem (adjusted OR = 0.12; p = 0.01). CONCLUSIONS: Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level significantly reduced the infant morbidity within the 24 weeks after birth in Bangladesh.

Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness.

Background: Transplacental respiratory syncytial virus (RSV) antibody transfer has been characterized, but little is known about the protective effect of breast milk RSV-specific antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F) exhibit high neutralizing activity. We investigate protection of breast milk pre-F antibodies against RSV acute respiratory infection (ARI). Methods: Breast milk at 1, 3, and 6 months postpartum and midnasal swabs during infant illness episodes were collected in mother-infant pairs in Nepal. One hundred seventy-four infants with and without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F immunoglobulin A (IgA) and immunoglobulin G (IgG) antibody levels were measured in breast milk. Results: The median breast milk pre-F IgG antibody concentration before illness was lower in mothers of infants with RSV ARI (1.4 [interquartile range {IQR}, 1.1-1.6] log10 ng/mL) than without RSV ARI (1.5 [IQR, 1.3-1.8] log10 ng/mL) (P = .001). There was no difference in median maternal pre-F IgA antibody concentrations in cases vs controls (1.7 [IQR, 0.0-2.2] log10 ng/mL vs 1.7 [IQR, 1.2-2.2] log10 ng/mL, respectively; P = .58). Conclusions: Low breast milk pre-F IgG antibodies before RSV ARI support a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines.

Impact of Timing of Influenza Vaccination in Pregnancy on Transplacental Antibody Transfer, Influenza Incidence, and Birth Outcomes: A Randomized Trial in Rural Nepal.

Background: Maternal influenza vaccination protects mothers and their infants in low resource settings, but little is known about whether the protection varies by gestational age at vaccination. Methods: Women of childbearing age in rural southern Nepal were surveilled for pregnancy, consented and randomized to receive maternal influenza vaccination or placebo, with randomization stratified on gestational age (17-25 or 26-34 weeks). Enrollment occurred in 2 annual cohorts, and vaccinations occurred from April 2011 through September 2013. Results: In sum, 3693 women consented and enrolled, resulting in 3646 live births. Although cord blood antibody titers and the rise in maternal titers were generally greater when women were vaccinated later in pregnancy, this was not statistically significant. The incidence risk ratio (IRR) for maternal influenza in pregnancy through 6 months postpartum was 0.62 (95% confidence interval [CI]: 0.35, 1.10) for those vaccinated 17-25 weeks gestation and 0.89 (95% CI: 0.39, 2.00) for those 26-34 weeks. Infant influenza IRRs were 0.73 (95% CI: 0.51, 1.05) for those whose mothers were vaccinated earlier in gestation, and 0.63 (95% CI: 0.37, 1.08) for those later. Relative risks (RR) for low birthweight were 0.83 (95% CI: 0.71, 0.98) and 0.90 (95% CI: 0.72, 1.12) for 17-25 and 26-34 weeks gestation at vaccination, respectively. IRRs did not differ for small-for-gestational age or preterm. No RRs were statistically different by timing of vaccine receipt. Conclusions: Vaccine efficacy did not vary by gestational age at vaccination, making maternal influenza immunization programs easier to implement where women present for care late in pregnancy. Clinical Trials Registration: NCT01034254.

Burden and Risk Factors for Coronavirus Infections in Infants in Rural Nepal.

Background: Knowledge of risk factors for symptomatic human coronavirus (HCoV) infections in children in community settings is limited. We estimated the disease burden and impact of birth-related, maternal, household, and seasonal factors on HCoV infections among children from birth to 6 months old in rural Nepal. Methods: Prospective, active, weekly surveillance for acute respiratory infections (ARIs) was conducted in infants over a period of 3 years during 2 consecutive, population-based randomized trials of maternal influenza immunization. Midnasal swabs were collected for acute respiratory symptoms and tested for HCoV and other viruses by reverse-transcription polymerase chain reaction. Association between HCoV incidence and potential risk factors was modeled using Poisson regression. Results: Overall, 282 of 3505 (8%) infants experienced an HCoV ARI within the first 6 months of life. HCoV incidence overall was 255.6 (95% confidence interval [CI], 227.3-286.5) per 1000 person-years, and was more than twice as high among nonneonates than among neonates (incidence rate ratio [IRR], 2.53; 95% CI, 1.52-4.21). HCoV ARI incidence was also positively associated with the number of children <5 years of age per room in a household (IRR, 1.13; 95% CI, 1.01-1.28). Of the 296 HCoV infections detected, 46% were coinfections with other respiratory viruses. While HCoVs were detected throughout the study period, seasonal variation was also observed, with incidence peaking in 2 winters (December-February) and 1 autumn (September-November). Conclusions: HCoV is associated with a substantial proportion of illnesses among young infants in rural Nepal. There is an increased risk of HCoV infection beyond the first month of life.

Vitamin A Supplementation during Pregnancy Enhances Pandemic H1N1 Vaccine Response in Mothers, but Enhancement of Transplacental Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy.

Background: In the growing embryo, the vitamin A requirement is tightly regulated. Maternal vitamin A deficiency during pregnancy may alter maternal immune function to accommodate the fetus. Objective: Our primary objective was to determine the effect of oral vitamin A supplementation (VAS) during pregnancy and until 6 mo postpartum on pandemic H1N1-vaccine responses in mothers and their infants at 6 mo of age. Methods: In this randomized controlled clinical trial, pregnant women (n = 112) during the second trimester (mean ± SD: 14 ± 1 wk) were assigned to receive either an oral dose of 10,000 IU vitamin A or placebo weekly until 6 mo postpartum. During the third trimester, mothers received a single dose of inactivated pandemic H1N1-influenza vaccine. Hemagglutination-inhibition (HAI) titer was measured in cord, infant, and maternal blood samples. Multivariate regressions with adjustments were used for data analysis. Results: Seventy-six percent of women had low plasma retinol concentrations (<1.05 µmol/L) in their second trimester. VAS of mothers increased vitamin A concentrations in cord blood by 21.4% and in colostrum by 40.7%. At 6 mo postpartum, women in the vitamin A group had 38.7% higher HAI titers and a higher proportion of HAI titer of ≥1:40 of the cutoff compared with the placebo group. A total of 54.5% of infants had an HAI titer ≥1:40 at 6 mo of age, but there was no difference in HAI titer in infants between groups. Overall, HAI in cord blood did not differ between groups, but in the placebo group, cord blood HAI was negatively associated with maternal "vaccination-to-delivery intervals" (rs = -0.401; P = 0.5), and maternal VAS increased cord blood HAI 6-fold if antenatal immunization was administered ≥10 wk before delivery. Conclusions: In a community with low vitamin A status, weekly maternal VAS during pregnancy and postpartum increases the breast-milk vitamin A concentration and enhances prenatal H1N1-vaccine responses in mothers, but the benefits of maternal VAS in transplacental antibody transfer may depend on the time of gestation when mothers were vaccinated. This trial was registered at clinicaltrials.gov as NCT00817661.

Human Metapneumovirus and Other Respiratory Viral Infections during Pregnancy and Birth, Nepal.

Human metapneumovirus (HMPV) is a respiratory virus that can cause severe lower respiratory tract disease and even death, primarily in young children. The incidence and characteristics of HMPV have not been well described in pregnant women. As part of a trial of maternal influenza immunization in rural southern Nepal, we conducted prospective, longitudinal, home-based active surveillance for febrile respiratory illness during pregnancy through 6 months postpartum. During 2011-2014, HMPV was detected in 55 of 3,693 women (16.4 cases/1,000 person-years). Twenty-five women were infected with HMPV during pregnancy, compared with 98 pregnant women who contracted rhinovirus and 7 who contracted respiratory syncytial virus. Women with HMPV during pregnancy had an increased risk of giving birth to infants who were small for gestational age. An intervention to reduce HMPV febrile respiratory illness in pregnant women may have the potential to decrease risk of adverse birth outcomes in developing countries.

Maternal Influenza Immunization and Adverse Birth Outcomes: Using Data and Practice to Inform Theory and Research Design.

Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol 2016;184(3):227-232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy.

Lung Ultrasonography: A Viable Alternative to Chest Radiography in Children with Suspected Pneumonia?

OBJECTIVE: To determine the interrater reliability (IRR) of lung ultrasonography (LUS) and chest radiography (CXR) and evaluate the accuracy of LUS compared with CXR for detecting pediatric pneumonia compared with chest computed tomography (CT) scan. STUDY DESIGN: This was a prospective cohort study of children aged 3 months to 18 years with a CXR and LUS performed between May 1, 2012, and January 31, 2014 with or without a clinical diagnosis of pneumonia. Four pediatric radiologists blinded to clinical information reported findings for the CXR and LUS images. IRR was estimated for 50 LUS and CXR images. The main outcome was the finding from CT ordered clinically or the probability of the CT finding for patients clinically requiring CT. Two radiologists reviewed CT scans to determine an overall finding. Latent class analysis was used to evaluate the sensitivity and specificity for findings (eg, consolidation) for LUS and CXR compared with CT. RESULTS: Of the 132 patients in the cohort, 36 (27%) had CT performed for a clinical reason. Pneumonia was clinically documented in 47 patients (36%). The IRR for lung consolidation was 0.55 (95% CI, 0.40-0.70) for LUS and 0.36 (95% CI, 0.21-0.51) for CXR. The sensitivity for detecting consolidation, interstitial disease, and pleural effusion was statistically similar for LUS and CXR compared with CT; however, specificity was higher for CXR. The negative predictive value was similar for CXR and LUS. CONCLUSIONS: LUS has a sufficiently high IRR for detection of consolidation. Compared with CT, LUS and CXR have similar sensitivity, but CXR is more specific for findings indicating pneumonia.

Designs of two randomized, community-based trials to assess the impact of influenza immunization during pregnancy on respiratory illness among pregnant women and their infants and reproductive outcomes in rural Nepal.

BACKGROUND: Among the most important causes of illness and death in both pregnant women and their newborn infants are respiratory infections including influenza. Pregnant women in North America have a 4 to 5 fold excess rate of hospitalization compared to non-pregnant women. Rates of infant hospitalization associated with influenza are much higher than in their mothers. Fully half of children hospitalized for influenza in the US are in the age group 0-5 months, a group where no vaccine is licensed. Data on influenza are much fewer in low income countries where the risks of serious morbidity and mortality are much higher. A recent trial in Bangladesh suggested that influenza immunization in pregnant women could have important protective effects against influenza in both mothers and their infants. These trials were designed to provide additional evidence about the effect of influenza vaccination in pregnancy in settings where influenza may circulate for up to ten months/year. METHODS/DESIGN: We conducted a consecutive pair of community-based, placebo-controlled, randomized trials of influenza vaccination of pregnant women in a rural district in southern Nepal. Two trials were conducted to insure, as much as possible, the match of circulating strains with those included in the vaccine. Eligible women included all who were or became pregnant over a one year period. Each trial included a one year cohort of pregnant women who were individually randomized to the influenza vaccine available at the time of their enrollment or placebo. Exclusions included a history of allergy to vaccine components, prior influenza vaccine receipt, and for the second trial, participation in the first trial. Morbidity was assessed on a weekly basis for women throughout pregnancy and through 180 days post-partum. Infants were followed weekly through 180 days. Primary outcomes included: 1) incidence of influenza like illness in women, 2) incidence of laboratory confirmed influenza illness in infants, and 3) birthweight among newborn infants. DISCUSSION: We have presented the design and methods of two randomized trials of influenza immunization of pregnant women. TRIAL REGISTRATION: Clinicaltrials.gov: ( NCT01034254 ).

Respiratory syncytial virus transplacental antibody transfer and kinetics in mother-infant pairs in Bangladesh.

BACKGROUND: Pneumonia is the leading cause of childhood mortality globally. Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia. Maternal serum antibody protects infants from RSV disease. The objective of our study was to characterize RSV antibody levels in mother-infant pairs. METHODS: Serial serum samples were collected from mother-infant pairs in Bangladesh from the third trimester of pregnancy to 72 weeks postpartum and tested using an RSV antibody microneutralization assay. Serologic infection was defined as a 4-fold increase in antibody titer. Maternal antibody half-life was calculated using infant antibody titers from birth to 20 weeks. RESULTS: The ratio of infant cord blood to maternal serum RSV antibody titers in 149 mother-infant pairs was 1.01 (95% confidence interval [CI], .99-1.03). Maternal RSV antibody titers in the third trimester and at birth were strongly correlated (R = 0.68). Antibody half-life was 38 days (95% CI, 36-42 days). Higher cord blood RSV antibody titers were associated with a lower risk of serologic infection (P = .01) and maintenance of antibody titer above a potentially protective threshold (P < .001). CONCLUSIONS: Efficient transplacental transfer of RSV-specific antibody from mother to the fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody titers were associated with protection from serologic infection.

Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis.

BACKGROUND: Guidelines do not currently recommend the use of lung ultrasound (LUS) as an alternative to chest X-ray (CXR) or chest computerized tomography (CT) scan for the diagnosis of pneumonia. We conducted a meta-analysis to summarize existing evidence of the diagnostic accuracy of LUS for pneumonia in adults. METHODS: We conducted a systematic search of published studies comparing the diagnostic accuracy of LUS against a referent CXR or chest CT scan and/or clinical criteria for pneumonia in adults aged ≥18 years. Eligible studies were required to have a CXR and/or chest CT scan at the time of evaluation. We manually extracted descriptive and quantitative information from eligible studies, and calculated pooled sensitivity and specificity using the Mantel-Haenszel method and pooled positive and negative likelihood ratios (LR) using the DerSimonian-Laird method. We assessed for heterogeneity using the Q and I2 statistics. RESULTS: Our initial search strategy yielded 2726 articles, of which 45 (1.7%) were manually selected for review and 10 (0.4%) were eligible for analyses. These 10 studies provided a combined sample size of 1172 participants. Six studies enrolled adult patients who were either hospitalized or admitted to Emergency Departments with suspicion of pneumonia and 4 studies enrolled critically-ill adult patients. LUS was performed by highly-skilled sonographers in seven studies, by trained physicians in two, and one did not mention level of training. All studies were conducted in high-income settings. LUS took a maximum of 13 minutes to conduct. Nine studies used a 3.5-5 MHz micro-convex transducer and one used a 5-9 MHz convex probe. Pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 94% (95% CI, 92%-96%) and 96% (94%-97%), respectively; pooled positive and negative LRs were 16.8 (7.7-37.0) and 0.07 (0.05-0.10), respectively; and, the area-under-the-ROC curve was 0.99 (0.98-0.99). CONCLUSIONS: Our meta-analysis supports that LUS, when conducted by highly-skilled sonographers, performs well for the diagnosis of pneumonia. General practitioners and Emergency Medicine physicians should be encouraged to learn LUS since it appears to be an established diagnostic tool in the hands of experienced physicians.

Combined effects of antenatal receipt of influenza vaccine by mothers and pneumococcal conjugate vaccine receipt by infants: results from a randomized, blinded, controlled trial.

A 2 × 2 factorial trial was performed to determine the efficacy of antennal influenza vaccination of mothers plus pneumococcal conjugate vaccination of their infants against respiratory illness during early infancy. The efficacy of trivalent inactivated influenza vaccine (TIV; delivered to mothers) plus 7-valent pneumococcal vaccine (PCV7; delivered to infants) was higher than the efficacy of TIV alone or PCV7 alone. During the period of the study in which influenza was circulating, the efficacy of TIV plus PCV7 was 72.4% (95% confidence interval, 30.2%-89.1%) against febrile respiratory illness and 66.4% (95% CI, 14.3%-86.9%) against medically attended acute respiratory illness.

Neonatal outcomes after antenatal influenza immunization during the 2009 H1N1 influenza pandemic: impact on preterm birth, birth weight, and small for gestational age birth.

BACKGROUND: Influenza infection during pregnancy is associated with adverse fetal outcomes such as preterm birth and small for gestational age (SGA). Maternal influenza immunization may prevent these adverse infant outcomes during periods of influenza circulation. METHODS: We conducted a retrospective cohort study of live births within Kaiser Permanente (KP) Georgia and Mid-Atlantic States (n = 3327) during the period of 2009 influenza A (H1N1) virus circulation. Primary outcomes were third-trimester preterm birth (27-36 weeks), birth weight, low birth weight (LBW, <2500 g), and SGA. RESULTS: There were 327 (9.8%) preterm, 236 (7.4%) LBW, and 267 (8.4%) SGA births. Among H1N1-vaccinated mothers (n = 1125), there were 86 (7.6%) preterm, 68 (6.4%) LBW, and 99 (9.3%) SGA births, and the mean birth weight was 3308.5 g (95% confidence interval [CI], 3276.6-3340.4). Among unvaccinated mothers (n = 1581), there were 191 (12.1%) preterm, 132 (8.8%) LBW, and 123 (8.2%) SGA births, and the mean birth weight was 3245.3 g (95% CI, 3216.5-3274.2). Infants of H1N1-vaccinated mothers had 37% lower odds of being born preterm than infants of unvaccinated mothers (adjusted odds ratio, 0.63 [95% CI, .47-.84]). The mean birth weight difference between infants of H1N1-vaccinated mothers and infants of unvaccinated mothers was 45.1 g (95% CI, 1.8-88.3). There was no significant association between maternal H1N1 influenza immunization and LBW or SGA. CONCLUSIONS: Pregnant women who received H1N1 influenza vaccine were less likely to give birth preterm, and gave birth to heavier infants. The findings support US vaccine policy choices to prioritize pregnant women during the 2009 influenza A (H1N1) pandemic.

Pregnancy modifies the antibody response to trivalent influenza immunization.

We report the immunogenicity of trivalent influenza immunization in 29 pregnant women compared with 22 nonpregnant women. We obtained blood specimens on day 0 prior to 2011-2012 influenza vaccine administration and day 28 after immunization. Hemagglutination inhibition (HAI) geometric mean titers were similar before immunization but were significantly reduced by 40%-50% in pregnant women after immunization for influenza A/California(H1N1) (P = .027) and A/Perth(H3N2) (P = .037). Postimmunization HAI titers were similar between groups for influenza B/Brisbane (P = .390). The geometric mean ratio (fold increase) for influenza A(H1N1) was nonsignificantly reduced in pregnant participants (P = .089). The percentages of participants who seroconverted and achieved seroprotection were similar between groups.

Detection and serotyping of lyophilized nonculturable pneumococcal isolates.

One hundred fifty-two nonculturable lyophilized carriage pneumococcal isolates from a vaccine trial were subjected to PCR for serotyping, and 149 (98%) were successfully classified as vaccine or nonvaccine types, which were similar to viable isolates. The methodology will be useful for analysis of this and other studies where stored pneumococcal isolates fail to grow.

A review of fetal and infant protection associated with antenatal influenza immunization.

The well-described burden of influenza morbidity in the pregnant woman and her young infant have led to increasing interest in the use of antenatal immunization to protect both the mother and the infant. In this review, we summarize the recent data on the effect of antenatal influenza infection, and influenza immunization, on mothers and infants. Antenatal influenza immunization can improve intrauterine growth in Asia and North America and reduce preterm deliveries. Studies of the pathogenetic process of influenza infection in the mother and fetus are needed. These findings suggest the wider use of antenatal immunization should be encouraged, including in low-resource regions. Creative approaches to antenatal influenza immunization policy should be developed to provide protection to the maternal, fetal, and infant triad in temperate and tropical regions.

Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial.

BACKGROUND: There are limited data about the effect of maternal influenza infection on fetuses and newborns. We performed a secondary analysis of data from the Mother's Gift project, a randomized study designed to test the effectiveness of inactivated influenza and pneumococcal vaccines during pregnancy. METHODS: In the Mother's Gift project, 340 pregnant women in Bangladesh received either inactivated influenza vaccine or 23-valent pneumococcal polysaccharide vaccine (control). This study was performed from August 2004 through December 2005. We performed a secondary analysis of outcomes following maternal influenza immunization during two periods: when influenza virus was not circulating (September 2004 through January 2005) and when influenza virus was circulating (February through October 2005). We assessed gestational age, mean birth weight and the proportion of infants who were small for gestational age. RESULTS: During the period with no circulating influenza virus, there were no differences in the incidence of respiratory illness with fever per 100 person-months among mothers and infants in the two groups (influenza vaccine: 3.9; control: 4.0; p > 0.9). The proportion of infants who were small for gestational age and the mean birth weight were similar between groups (small for gestational age: influenza vaccine 29.1%, control 34.3%; mean birth weight: influenza vaccine 3083 g, control 3053 g). During the period with circulating influenza virus, there was a substantial reduction in the incidence per 100 person-months of respiratory illness with fever among the mothers and infants who had received the influenza vaccine (influenza vaccine: 3.7; control: 7.2; p = 0.0003). During this period, the proportion of infants who were small for gestational age was lower in the influenza vaccine group than in the control group (25.9% v. 44.8%; p = 0.03). The mean birth weight was higher among infants whose mothers received the influenza vaccine than among those who received the control vaccine during this period (3178 g v. 2978 g; p = 0.02). INTERPRETATION: During the period with circulating influenza virus, maternal immunization during pregnancy was associated with a lower proportion of infants who were small for gestational age and an increase in mean birth weight. These data need confirmation but suggest that prevention of influenza infection in pregnancy can influence intrauterine growth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT 00142389.

Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study.

BACKGROUND: Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births. METHODS AND FINDINGS: We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October-31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38-0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26-0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11-0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13-0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period. CONCLUSIONS: This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth.

Effectiveness of maternal influenza immunization in mothers and infants.

BACKGROUND: Young infants and pregnant women are at increased risk for serious consequences of influenza infection. Inactivated influenza vaccine is recommended for pregnant women but is not licensed for infants younger than 6 months of age. We assessed the clinical effectiveness of inactivated influenza vaccine administered during pregnancy in Bangladesh. METHODS: In this randomized study, we assigned 340 mothers to receive either inactivated influenza vaccine (influenza-vaccine group) or the 23-valent pneumococcal polysaccharide vaccine (control group). Mothers were interviewed weekly to assess illnesses until 24 weeks after birth. Subjects with febrile respiratory illness were assessed clinically, and ill infants were tested for influenza antigens. We estimated the incidence of illness, incidence rate ratios, and vaccine effectiveness. RESULTS: Mothers and infants were observed from August 2004 through December 2005. Among infants of mothers who received influenza vaccine, there were fewer cases of laboratory-confirmed influenza than among infants in the control group (6 cases and 16 cases, respectively), with a vaccine effectiveness of 63% (95% confidence interval [CI], 5 to 85). Respiratory illness with fever occurred in 110 infants in the influenza-vaccine group and 153 infants in the control group, with a vaccine effectiveness of 29% (95% CI, 7 to 46). Among the mothers, there was a reduction in the rate of respiratory illness with fever of 36% (95% CI, 4 to 57). CONCLUSIONS: Inactivated influenza vaccine reduced proven influenza illness by 63% in infants up to 6 months of age and averted approximately a third of all febrile respiratory illnesses in mothers and young infants. Maternal influenza immunization is a strategy with substantial benefits for both mothers and infants. (ClinicalTrials.gov number, NCT00142389.)

Interactions of diarrhea, pneumonia, and malnutrition in childhood: recent evidence from developing countries.

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 children's 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 children's 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.