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

BACKGROUND: Maternal 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. METHODS: We 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. FINDINGS: 10 002 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. INTERPRETATION: The 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. FUNDING: Bill & Melinda Gates Foundation.

Parents' Perspectives on Supporting Father Involvement in African American Families During Pregnancy and Early Infancy.

OBJECTIVE: To explore fathers' pregnancy and early infancy experiences in supporting his infant, partner, and himself, using information collected from fathers, mothers, and mother-father dyads in a low-income, urban community. BACKGROUND: Father involvement is associated with positive child health outcomes and parental well-being. However, little information exists about low-income parents' perceived needs for father involvement during pregnancy and infancy. METHODS: This was an exploratory qualitative study of parents in low-income communities of Baltimore, Maryland. Participants were conveniently sampled via partnerships with community organizations. Eighty percent of parents were African American. Four focus groups were conducted with fathers (n = 8), 4 with mothers (n = 9), and 4 interviews with father-mother dyads (n = 8). Sessions were audio-recorded, transcribed, and analyzed using iterative, inductive open coding performed independently by two team members (interrater agreement 86%). Frequency tables were generated for identified categories for content analysis and theme development. RESULTS: Five themes were identified: perspectives on the father role, supporting partners, negotiating co-parenting, parenting logistics, and learning parenting skills. Participants expressed the importance of fathers to "be there" and barriers to being involved (e.g., finances, lack of role models). Fathers discussed needing to learn how to manage partner conflicts, while mothers discussed fathers' need for greater empathy. Dyads discussed the importance of co-parenting strategies (e.g., effective communication, sharing responsibilities). Logistics included direct infant care, finances, and community resources. Fathers discussed learning by trial and error rather than informational resources and relying on healthcare professionals for pregnancy information and female relatives for infant care. CONCLUSION: Participants discussed various needs of fathers to be effective partners and parents, and lacking informational resources tailored specifically for fathers. Research is needed to explore the best ways to tailor and disseminate information to fathers, especially prenatally. IMPLICATIONS: Study findings have significant implications for improving the ways in which maternity care, community-based programs, and pediatric providers support father involvement.

Maternal Influenza Immunization and Prevention of Severe Clinical Pneumonia in Young Infants: Analysis of Randomized Controlled Trials Conducted in Nepal, Mali and South Africa.

BACKGROUND: To evaluate the effect of antenatal influenza vaccination on all-cause severe infant pneumonia, we performed pooled analysis of 3 randomized controlled trials conducted in Nepal, Mali and South Africa. METHODS: The trials were coordinated from the planning phase. The follow-up period was 0-6 months postpartum in Nepal and Mali and 0-24 weeks in South Africa. Pregnant women with gestational age 17-34 weeks in Nepal, ≥28 weeks in Mali and 20-36 weeks in South Africa were enrolled. Trivalent inactivated influenza vaccine (IIV) was compared with either saline placebo (Nepal and South Africa) or quadrivalent meningococcal conjugate vaccine (Mali). In South Africa, cases were hospitalized and were therefore considered to have severe pneumonia. In Nepal and Mali, severe infant pneumonia diagnosis was based on the WHO Integrated Management of Childhood Illness definition. RESULTS: A total of 10,002 mothers and 9801 live-born eligible infants were included in the present analysis. There was a 31% lower incidence rate of severe pneumonia in the IIV group compared with the control group in Nepal [incidence rate ratio (IRR): 0.69; 95% CI: 0.50-0.94; ]. In South Africa, there was a 43% lower incidence rate of severe pneumonia in the IIV group versus the control group (IRR: 0.57; 95% CI: 0.33-1.0). There was no difference in incidence rates between the IIV group and the control group in Mali. Overall, incidence rate of severe pneumonia was 20% lower in the IIV group compared with the control group (IRR: 0.80; 95% CI: 0.66-0.99; P = 0.04). Protection was highest in the high influenza circulation period (IRR: 0.44; 95% CI: 0.23-0.84). CONCLUSIONS: Maternal influenza immunization may reduce severe pneumonia episodes among infants-particularly those too young to be completely vaccinated against Streptococcus pneumoniae and influenza.

The Effects of Influenza Vaccination during Pregnancy on Birth Outcomes: A Systematic Review and Meta-Analysis.

Objective Numerous observational studies have evaluated the relationship between influenza vaccination during pregnancy and birth outcomes. The number of studies on this subject has increased, especially after the 2009 A/H1N1 pandemic (A/H1N1pdm09). This meta-analysis aims to determine the impact of maternal vaccination with either seasonal trivalent inactivated influenza vaccines (IIV) or A/H1N1pdm09 monovalent vaccines on the rates of preterm (PTB), small for gestational age (SGA), and low birth weight (LBW) births. Methods English language randomized controlled trials and observational studies assessing the proposed outcomes after administration of influenza vaccine during pregnancy were screened. Observational studies were included if they presented adjusted measures and if the total number of women evaluated reached predefined thresholds. Sensitivity analyses were performed, including all published observational studies irrespectively of the sample size. Results A total of 5 and 13 publications that assessed the impact of IIV and monovalent A/H1N1pdm09 vaccines, respectively, fulfilled the inclusion criteria for the main analyses. The rate of PTB and LBW was lower in women who received IIV during pregnancy compared with nonvaccinated women (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77, 0.98 for PTB and OR: 0.74; 95% CI: 0.61, 0.88 for LBW); and in women vaccinated with monovalent A/H1N1pdm09 versus nonvaccinated women (OR: 0.92; 95% CI: 0.85, 0.99 for PTB and OR: 0.88; 95% CI: 0.79, 0.98 for LBW). No significant impact of vaccination on SGA birth rates was detected in the main analyses independently of the vaccine group. Conclusion Receipt of influenza vaccine during pregnancy was associated with a decreased risk of PTB and LBW.

Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations.

Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization.