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

Richards, Jennifer L. (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/td96k315k?locale=en
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Abstract

Abstract

Context: 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 seasonal influenza circulation. There are no published studies on the effect of maternal influenza immunization on adverse infant outcomes during the 2009 influenza A (H1N1) influenza pandemic.

Objective: To evaluate the association between maternal influenza immunization and third trimester preterm birth, low birth weight, and SGA during the 2009 influenza A (H1N1) pandemic.

Design, Setting, Participants: Retrospective cohort study including 3,327 live births within Kaiser Permanente (KP) Georgia and Mid-Atlantic States during the period of 2009 influenza A (H1N1) virus circulation (April 26, 2009 to April 17, 2010). We used KP electronic medical records to identify influenza vaccinations, outcomes, and covariates.

Main outcome measures: Primary outcomes were third trimester preterm birth (27-36 weeks), birth weight, low birth weight (<2500 grams), and small for gestational age.

Results: Infants whose mothers were vaccinated against H1N1 influenza had 36% lower odds of being born preterm than infants of unvaccinated mothers (aOR: 0.64, 95% CI: 0.48-0.85). Infants whose mothers were vaccinated against H1N1 influenza were 55.6 grams (95% CI: 12.4, 98.8) heavier, on average, than infants in the no vaccine group (3364.8 grams versus 3309.2 grams). There was no significant association between maternal H1N1 influenza immunization and low birth weight or SGA.

Conclusions: This is the first study to evaluate the effect of 2009 H1N1 influenza vaccine on preterm birth, birth weight, and SGA. Maternal influenza immunization was associated with reduced odds of third trimester preterm birth during the 2009 influenza A (H1N1) pandemic. Infants of mothers who received 2009 H1N1 influenza vaccine weighed more at birth, on average, than infants born to unvaccinated mothers.

Table of Contents

Contents

Background 1

Influenza 1

Pregnancy Physiology and Adverse Infant Outcomes 2

Influenza Infection during Pregnancy 4

2009 Influenza A (H1N1) Pandemic Influenza during Pregnancy 6

Influenza Vaccine 8

Influenza Vaccine Coverage in Pregnant Women 9

Evidence Base for Maternal Influenza Immunization 10

Addressing Confounding in Nonrandomized Influenza Vaccine Effectiveness Studies 12

Addressing Limitations of Observational Studies of Influenza Vaccine Effectiveness in Managed Care Organization Populations 14

References 17

Draft Manuscript 21

Introduction 22

Methods 22

Results 26

Discussion 27

Tables and Figures 32

Figure 1. Definition of primary analysis cohort. 33

Figure 2. Influenza vaccine coverage among mothers of infants born during period of 2009 influenza A (H1N1) circulation, by infant's birth month. 34

Table 1. Influenza vaccine exposure among mothers of infants born during period of 2009 influenza A (H1N1) circulation, overall and by Kaiser Permanente site. 35

Table 2. Receipt of influenza vaccine during pregnancy categorized by maternal characteristics and type of vaccine received. 36

Table 3. ORs for association of maternal influenza immunization with infant outcomes, among infants born during period of 2009 influenza A (H1N1) virus circulation. 37

Table 4. Comparison of birth weight among infants born during period of 2009 influenza A (H1N1) virus circulation, by mother's influenza vaccine status. 38

References 39

Supplementary Materials 43

Supplement 1: Classification of Influenza Vaccines Administered to Study Mothers 44

Supplementary Table 1. Sensitivity analyses of ORs for association of maternal influenza immunization with infant outcomes, among infants born during period of 2009 influenza A (H1N1) virus circulation, using alternative vaccine definition algorithm. 46

Supplement 2: Definition of Pregnancy Period for Classification of Vaccine Exposure 47

Supplementary Table 2. Sensitivity analyses of ORs for association of maternal influenza immunization with infant outcomes, among infants born during period of 2009 influenza A (H1N1) virus circulation, defining influenza vaccination during pregnancy as being vaccinated between LMP and at least 7 days prior to birth. 48

Supplementary Table 3. Sensitivity analyses of ORs for association of maternal influenza immunization with infant outcomes, among infants born during period of 2009-2010 H1N1 influenza circulation, defining influenza vaccination during pregnancy as being vaccinated between LMP and at least 14 days prior to birth. 49

Public Health Implications 50

Long-Term Implications of Adverse Infant Outcomes 50

How This Study Adds to Maternal Influenza Immunization Research 51

Maternal Immunization as Feasible Strategy for Addressing Risk of Adverse Infant Outcomes 52

Future Research and Data Needs 52

References 55


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