First Trimester Influenza Vaccination and Risks for Major Structural Birth Defects in Offspring

Abstract

Objective: To examine risks for major structural birth defects in infants after first trimester inactivated influenza vaccine (IIV) exposures.

Study design: In this observational study, we used electronic health data from 7 Vaccine Safety Datalink sites to examine risks for selected major structural defects in infants after maternal IIV exposure. Vaccine exposures for women with continuous insurance enrollment through pregnancy who delivered singleton live births between 2004 and 2013 were identified from standardized files. Infants with continuous insurance enrollment were followed to 1 year of age. We excluded mother-infant pairs with other exposures that potentially increased their background risk for birth defects. Selected cardiac, orofacial or respiratory, neurologic, ophthalmologic or otologic, gastrointestinal, genitourinary and muscular or limb defects were identified from diagnostic codes in infant medical records using validated algorithms. Propensity score adjusted generalized estimating equations were used to estimate prevalence ratios (PRs).

Results: We identified 52 856 infants with maternal first trimester IIV exposure and 373 088 infants whose mothers were unexposed to IIV during first trimester. Prevalence (per 100 live births) for selected major structural birth defects was 1.6 among first trimester IIV exposed versus 1.5 among unexposed mothers. The adjusted PR was 1.02 (95% CI 0.94-1.10). Organ system-specific PRs were similar to the overall PR.

Conclusion: First trimester maternal IIV exposure was not associated with an increased risk for selected major structural birth defects in this large cohort of singleton live births.

Figure 1.

Flow chart of identified pregnancies ending in a live birth and exclusion criteria used to obtain mother–infant cohort at 7 Vaccines Safety Datalink sites, January 1, 2004, to September 30, 2013. ^aContinuous insurance enrollment from 6 months before the last menstrual period (LMP) through 6 weeks postpartum. ^bMore than 1 medical condition may apply to a single pregnant female. ^cToxoplasmosis, syphilis, varicella, rubella, or cytomegalovirus. ^dAfter excluding no medical care within the healthcare system during pregnancy, medical condition, teratogenic medication, or live virus vaccine. ^eincludes infants with mortality during the first year of life and infants hospitalized for more than 30 days after birth who were not required to meet insurance enrollment criteria. ^fFor infants surviving to 1 year, enrollment in a health insurance plan for 4 months during the first year and at least 1 month of insurance in the first 3 months of life.

Figure 2.

Histogram of estimated week at last menstrual period (LMP) by vaccination status, for the final study cohort, across 10 influenza seasons. A, Women who did not receive IIV during first trimester. B, Women vaccinated with IIV during first trimester. Week 0 corresponds to the week starting January 1, 2003. Peaks in first trimester IIV administration, by week of LMP, by influenza season, were as follows: 2003-2004 (LMP = week 37 or September 8, 2003); 2004-2005 (LMP = week 85 or August 9, 2004); 2005-2006 (LMP = week 139 or August 29, 2005); 2006-2007 (LMP = week 190 or August 21, 2006); 2007-2008 (LMP = week 243 or August 27, 2007); 2008-2009 (LMP = week 297 or September 8, 2008); 2009-2010 (LMP = week 343 or July 27, 2009); 2010-2011 (LMP = week 400 or September 6, 2010); 2011-2012 (LMP = week 450 or August 22, 2011); and 2012-2013 (LMP = week 504 or September 3, 2012).