Impact of Influenza Vaccination during Pregnancy on Maternal Influenza Disease Severity in Rural Nepal.

Source: Rowe SL, Leder K, Perrett KP, et al. Maternal vaccination and infant influenza and pertussis. Pediatrics. 2021;148(3): e2021051076; doi.10.1542/peds.2021-051076Investigators from multiple institutions in Australia conducted a population-level inception cohort study to assess the effectiveness of maternal influenza and pertussis vaccination during pregnancy in preventing these diseases in their children during the first 6 months of life. For the study, they abstracted data from the Victorian Perinatal Data Collection (VPDC) on women whose pregnancies ended between September 2015 and December 2017. The VPDC includes information on all live births and stillbirths in Victoria, Australia, including demographic and clinical data related to pregnancy and birth. In addition, whether the mother received influenza and/or pertussis vaccine at any time during pregnancy is recorded. Data from multiple databases were reviewed to identify laboratory-confirmed cases of influenza and pertussis in infants <6 months old during the study period and record ED visits, hospital admissions, and deaths from influenza and pertussis. Information from these databases and VPDC were linked to identify mother-infant dyads.The primary study outcomes were laboratory-confirmed cases of influenza and pertussis in infants born to mothers included in the study, and secondary outcomes included cases of severe disease, defined as ED visit, hospitalization, or death from influenza or pertussis in study infants. Poisson regression was used to calculate the relative risk (RR) for influenza and pertussis in infants of mothers vaccinated during pregnancy vs not vaccinated, after adjusting for multiple confounders. Results were stratified in infants <2 months old, and those 2 to <6 months of age. Vaccine effectiveness (VE) of maternal immunization in preventing childhood illness was estimated as (1-RR) × 100.Data were analyzed on 186,962 mother-infant dyads. Overall, 45.9% of study women were vaccinated against influenza during pregnancy and 68.5% against pertussis. There were 185,404 and 184,194 infants, respectively, included in influenza and pertussis vaccination analyzes. The risk of influenza was significantly reduced in children whose mothers were vaccinated, both among children <2 months old (RR, 0.44; 95% CI, 0.25, 0.77), and in those 2 to <6 months of age (RR, 0.64; 95% CI, 0.42, 0.98), with VE estimated as 56.1% (95% CI, 23.3%, 74.9%) and 35.7% (95% CI, 2.2%, 57.7%), respectively. Maternal vaccination reduced the risk of pertussis in infants <2 months old (RR, 0.20; 95% CI, 0.06, 0.63), with an estimated VE of 80.1% (95% CI, 37.1%, 93.7%), but no significant effect was noted among infants 2 to <6 months old (RR, 0.68; 95% CI, 0.33, 1.39). Maternal pertussis immunization reduced the risk of severe pertussis in infants <2 months old (RR, 0.38; 95% CI, 0.16, 0.94). There were no significant effects from maternal vaccination on severe cases of pertussis in children 2 to <6 months old or on influenza among children <6 months old.The authors conclude that maternal vaccination during pregnancy reduces the risk of influenza and pertussis in infants <2 months old.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The goal of maternal immunization is to provide infants with passive antibodies prior to their first dose of vaccines. In a previous study, Baxter et al1 noted that maternal Tdap during pregnancy significantly reduced pertussis risk during the entire first year of life (See AAP Grand Rounds. 2017;38[2]:15.)1 In the current study, which included infants born at ≥30 weeks’ gestation, this benefit was most notable only in infants <2 months. In contrast, Baxter et al1 enrolled only infants born at ≥37 weeks’ gestation, allowing more time for antibody transfer after maternal Tdap receipt (usually between 27–36 weeks’ gestation).2As demonstrated by the results of the current study, maternal vaccination during pregnancy also reduces the infant’s risk for influenza during the first 6 months of life. Tdap and influenza vaccination rates during pregnancy, however, remain suboptimal.3 To assess influenza and Tdap vaccination coverage among women pregnant during the 2020–21 influenza season, the Centers for Disease Control and Prevention (CDC) conducted a survey during April 2021.4 Among 1,795 survey respondents who were pregnant anytime during October 2020–January 2021, 54.5% reported receiving an influenza vaccine before or during pregnancy. Among 729 respondents, 53.5% reported receiving Tdap during pregnancy. Unfortunately, receipt of both influenza and Tdap vaccines was reported by only 30.7% of women.COVID-19 vaccines also are recommended for all pregnant women.5 Providers need to take every opportunity to recommend these vaccines for their pregnant patients.Vaccination of pregnant women with Tdap, influenza, and COVID-19 vaccines is safe and protects the mother and her young infant.As influenza vaccines are approved only for infants ≥6 months of age, the 6-month duration of immunity conferred by maternal influenza vaccination provides further support for maternal immunization.

Safety of influenza vaccines in pregnant women

Maternal pertussis and influenza immunization coverage and attitude of health care workers towards these recommendations in Flanders, Belgium

Maternal infections and fever during pregnancy are associated with increased risk for autism spectrum disorders (ASDs). To our knowledge, no study has investigated the association between influenza vaccination during pregnancy and ASD. To investigate the association between influenza infection and vaccination during pregnancy and ASD risk. This cohort study included 196 929 children born at Kaiser Permanente Northern California from January 1, 2000 to December 31, 2010, at a gestational age of at least 24 weeks. Data on maternal influenza infection and vaccination from conception date to delivery date, obtained from Kaiser Permanente Northern California inpatient and outpatient databases. Influenza infection was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification codes or positive influenza laboratory test results. Clinical diagnoses of ASDs identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes 299.0, 299.8, or 299.9 recorded in Kaiser Permanente Northern California electronic medical records on at least 2 occasions any time from birth through June 2015. Within this cohort of 196 929 children, influenza was diagnosed in 1400 (0.7%) mothers and 45 231 (23%) received an influenza vaccination during pregnancy. The mean (SD) ages of vaccinated and unvaccinated women were 31.6 (5.2) and 30.4 (5.6) years, respectively. A total number of 3101 (1.6%) children were diagnosed with ASD. After adjusting for covariates, we found that maternal influenza infection (adjusted hazard ratio, 1.04; 95% CI, 0.68-1.58) or influenza vaccination (adjusted hazard ratio, 1.10; 95% CI, 1.00-1.21) anytime during pregnancy was not associated with increased ASD risk. In trimester-specific analyses, first-trimester influenza vaccination was the only period associated with increased ASD risk (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39). However, this association could be due to chance (P = 0.1) if Bonferroni corrected for the multiplicity of hypotheses tested (n = 8). Maternal influenza vaccination in the second or third trimester was not associated with increased ASD risk. There was no association between maternal influenza infection anytime during pregnancy and increased ASD risk. There was a suggestion of increased ASD risk among children whose mothers received an influenza vaccination in their first trimester, but the association was not statistically significant after adjusting for multiple comparisons, indicating that the finding could be due to chance. These findings do not call for changes in vaccine policy or practice, but do suggest the need for additional studies on maternal influenza vaccination and autism.

Report of the WHO technical consultation on the effect of maternal influenza and influenza vaccination on the developing fetus: Montreal, Canada, September 30–October 1, 2015

Maternal influenza vaccination has increased birth weight in two randomized trials in South Asia but the impact on infant growth is unknown. A randomized placebo-controlled trial of year round maternal influenza immunization was conducted in two annual cohorts in Sarlahi District, southern plains of Nepal, from April 2011 through April 2014. Infants born to women enrolled in the trial had weight, length, and head circumference measured at birth and 6 months of age. The study was powered for the 3 primary trial outcomes but not for stunting and wasting at 6 months of age. 3693 women received placebo or influenza vaccine between 17 and 34 weeks gestation, resulting in 3646 live births. About 72% of infants who survived had weight and length measurements between 150 and 210 days of age. Prevalence of stunting (<-2 Z scores length-for-age) was 14.8% in the placebo and 13.6% in the vaccine groups, respectively. Stunting < -3 Z scores was 3.2% versus 2.0% in placebo versus vaccine groups (RR: 0.64 (95% CI: 0.39, 1.04)). Wasting (< -2 Z scores weight for length) was 10.3% versus 11.0% for placebo versus vaccine groups. Severe wasting (< -3 Z scores weight for length) was 3.8% for placebo versus 2.6% for vaccine (RR: 0.69 (95% CI: 0.44, 1.07)). The impact of flu vaccine on wasting was greater in cohort 2 than in cohort 1, (RR: 0.66 (0.44, 0.99) for any wasting), and RR: 0.45 (0.19, 1.09) for severe wasting. This corresponded to a larger impact on birth weight and a better vaccine match with circulating viruses in cohort 2. Although maternal immunization reduced low birth weight by 15%, only wasting at 6 months in the 2nd cohort was statistically significantly difference. However, the study was underpowered to detect reductions of public health importance. Clinicaltrials.gov (NCT01034254).

ObjectiveTo describe the effect of maternal vaccination on birth outcomes in rural Nepal, modified by timing of vaccination in pregnancy and influenza virus activity.MethodsA secondary analysis was conducted using data from two annual cohorts of a randomized controlled trial. A total of 3693 pregnant women from Sarlahi District were enrolled between April 25, 2011, and September 9, 2013. All participants were aged 15–40 years and received a trivalent inactivated influenza vaccine or placebo. The outcome measures included birth weight, pregnancy length, low birth weight (<2500 g), preterm birth, and small‐for‐gestational‐age birth.ResultsData were available on birth weight for 2741 births and on pregnancy length for 3623 births. Maternal vaccination increased mean birthweight by 42 g (95% confidence interval [CI] 8–76). The magnitude of this increase varied by season but was greatest among pregnancies with high influenza virus circulation during the third trimester. Birth weight increased by 111 g (95% CI −51 to 273) when 75%–100% of a pregnancy's third trimester had high influenza virus circulation versus 38 g (95% CI −6 to 81) when 0%–25% of a pregnancy's third trimester had high influenza virus circulation. However, these results were nonsignificant.ConclusionSeasonal maternal influenza vaccination in rural Nepal increased birth weight; the magnitude appeared larger during periods of high influenza virus circulation.ClinicalTrials.gov NCT01034254.

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. 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. 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. 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. NCT01034254.

No association between influenza vaccination during pregnancy and adverse birth outcomes

The coverage of maternal vaccination against pertussis and, particularly, influenza is lower than expected. The lack of recommendation from healthcare providers conditions non-vaccination in pregnant women. The purpose was to determine the knowledge, perceptions, attitudes and practices of midwives regarding maternal influenza and pertussis vaccination. A qualitative descriptive study based on semi-structured, face-to-face interviews with seventeen midwives was conducted, including purposive sampling and thematic analyses. Midwives had disparate knowledge and perceptions about the severity of influenza and pertussis in pregnant women, and influenza was not considered very serious. The vaccines were generally considered safe. However, because midwives did not have enough information about the safety of the influenza vaccine, there was a tendency not to recommend it. While most midwives had a positive attitude toward vaccination, their advocation for vaccination against influenza was not as clear as it was for pertussis. Not wanting to influence the decision and assuming an informative–facilitating role also led providers to recommend the influenza vaccine less frequently. Midwives are among the main sources of professional advice for pregnant women. Addressing their understanding and professional practices regarding maternal vaccination is key to change the attitude of pregnant women and thus increase vaccine uptake among them, particularly for influenza.

Maternal Tdap and influenza vaccination uptake 2017-2021 in the United States: Implications for maternal RSV vaccine uptake in the future

There is growing evidence that seasonal influenza vaccination in pregnancy has benefits for mother and baby. We determined influenza vaccination rates among pregnant women during the 2 nonpandemic influenza seasons following the 2009 H1N1 pandemic, explored maternal factors as predictors of influenza vaccination status and evaluated the association between maternal influenza vaccination and neonatal outcomes. We used a population-based perinatal database in the province of Nova Scotia, Canada, to examine maternal vaccination rates, determinants of vaccination status and neonatal outcomes. Our cohort included women who gave birth between Nov. 1, 2010, and Mar. 31, 2012. We compared neonatal outcomes between vaccinated and unvaccinated women using logistic regression analysis. Overall, 1958 (16.0%) of 12,223 women in our cohort received the influenza vaccine during their pregnancy. Marital status, parity, location of residence (rural v. urban), smoking during pregnancy and maternal influenza risk status were determinants of maternal vaccine receipt. The odds of preterm birth was lower among infants of vaccinated women than among those of nonvaccinated women (adjusted odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.94). The rate of low-birth-weight infants was also lower among vaccinated women (adjusted OR 0.73, 95% CI 0.56-0.95). Despite current guidelines advising all pregnant women to receive the seasonal influenza vaccine, influenza vaccination rates among pregnant women in our cohort were low in the aftermath of the 2009 H1N1 pandemic. This study and others have shown an association between maternal influenza vaccination and improved neonatal outcomes, which supports stronger initiatives to promote vaccination during pregnancy.

To determine whether influenza vaccination of pregnant women prevents visits for respiratory illness in their infants born during the influenza season. Retrospective matched cohort study. Four managed care organizations in the United States. Patients A total of 41 129 infants (3160 and 37 969 born to vaccinated and unvaccinated mothers, respectively) born between 1995 and 2001. Main Exposure Maternal influenza vaccination. Infants were considered exposed if their gestational age at birth was at least 30 weeks, if the time from maternal vaccination to birth was at least 28 days, and if they were exposed to at least 14 days of the influenza season. Incidence of acute respiratory illnesses (outpatient, emergency department, and inpatient settings combined) and incident rate ratios (IRRs) for infants exposed and unexposed to maternal vaccination during the following 4 periods: peak influenza, respiratory syncytial virus predominant, periseasonal, and summer weeks. The time to the first acute respiratory illness during peak influenza weeks was also assessed. During the peak influenza weeks, infant visit rates were 15.4 and 17.1 per 100 person-months for exposed and unexposed infants, respectively (IRR, 0.90; 95% confidence interval, 0.80-1.02). Adjusted IRRs for the 4 periods found a protective effect of infant female sex, whereas Medicaid status and maternal high-risk status increased infant visit rates. Maternal influenza vaccination did not reduce visit rates during any of the 4 time periods (IRR for peak influenza season, 0.96; 95% confidence interval, 0.86-1.07) and did not delay the onset of first respiratory illness. We were unable to demonstrate that maternal influenza vaccination reduces respiratory illness visit rates among their infants.

Translating vaccine policy into action: A report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings

Implementation of maternal influenza immunization in El Salvador: Experiences and lessons learned from a mixed-methods study