Influenza Vaccines and Birth Outcomes

Project Title Influenza Vaccines and Birth Outcomes
Date Posted
Wednesday, February 6, 2019

This project was a one-time assessment of the association between influenza vaccination and birth outcomes (cleft lip without cleft palate, cleft palate without cleft lip, or cleft lip with cleft palate).

Medical record review was conducted to confirm case status, confounders, and gestational age at delivery to better understand the strengths and limitations of using electronic data for surveillance. Protocol-based assessments use study designs and analysis plans customized for the product-outcome pairs being assessed.

The Mini-Sentinel Operations Center posted this protocol for public comment from February 25, 2013, through March 11, 2013. The public comment period is now closed.  A revised version was approved for implementation by FDA on December 5, 2014 and a second revised version was approved for implementation by FDA on January 3, 2017. A log of changes is included in the revised protocol (v3).

Medical Product
influenza vaccine
Health Outcome
cleft lip with cleft palate
cleft lip without cleft palate
cleft palate without cleft lip
Population / Cohort
Females 10-55 years of age
Time Period
January 2004 - May 2012
Assessment Type
Safety Analyses
Study Type
Protocol/Surveillance Plan
Workgroup Leader(s)

Alison Kawai ScD; Grace Lee MD, MPH; Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA

Azadeh Shoaibi PhD, MS, MHS; Center for Biologics Evaluation and Research, FDA, Silver Spring, MD

Workgroup Members

Carolyn Balsbaugh MPH; Austin Cosgrove; Sandra Feibelmann MPH; Katherine Freitas; Tim Glavin; Katie Haffenreffer; Margaret Johnson; MPH; Lingling Li PhD; Madelyn Pimentel; Linda Pointon; Megan Reidy MPH; Catherine Rogers MPH; Robert Rosofsky MA; Lauren Zichittella MS; Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, MA

Susan Andrade ScD; Meyers Primary Care Institute, a joint endeavor of Fallon Community Health Plan, Reliant Medical Group, and University of Massachusetts Medical School, Worcester, MA

Steve Anderson PhD, Faith Barash MD, MPH; Laura Polakowski MD, MPH; Office of Biostatistics and Epidemiology Center for Biostatistics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD

Vinit Nair BPharm; Mano Selvan PhD; Yunping Zhou MS; Comprehensive Health Insights, Humana, Louisville, KY

Michael Doherty MS; Laura Karslake MS; Ling Li MSPH; Nancy Lin ScD; Anita Loughlin PhD; Eva Ng MS; Rosie Prieto; Steve Roloff; Judy Wong; Li Zhou MS; OptumInsight Inc, Waltham, MA

Kirti Batra MS; Smita Bhatia MCA; Carolyn Jevit; Yihai Liu; Cheryl McMahill-Walraven MSW, PhD; Aetna Inc, Blue Bell, PA

Bola Ekezue PhD; Kevin Haynes PharmD; Chunfu Liu ScD; Mike Mack MS; Lauren Parlett PhD, Nandini Selvam, PhD, MPH; Sonali Shambhu MPH; Fang Tian PhD; HealthCore, Inc, Alexandria, VA,

Kecia Carroll MD, MPH; Vanderbilt University Medical Center, Nashville, TN

Erin Longley MD; Community Health Care, Lakewood, WA

Tara Wenger MD, PhD; Seattle Children’s Craniofacial Center, Seattle, WA

Data Sources
Mini-Sentinel Distributed Database (MSDD), immunization registries, and vital record registries in Colorado, Georgia, Pennsylvania, Missouri, Utah, Louisiana, Virginia, and Florida
FDA Center