1899. Lack of efficacy of trivalent influenza vaccination of HIV Negative pregnant women against adverse fetal outcomes: A Randomized Clinical Trial
Session: Poster Abstract Session: Vaccines: Influenza
Saturday, October 10, 2015
Room: Poster Hall
Background: Preventing stillbirth, low birth weight, small size for gestational age and prematurity are important potential effects of antenatal maternal immunization with influenza vaccines for which there are conflicting data from predominantly observational studies. 

Methods: A double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine (IIV3) was conducted in Soweto, South Africa from March 3, 2011 and was completed after the 2012 influenza season when the infants born had reached the age of 24 weeks.  An objective was to evaluate the efficacy of IIV3 during pregnancy against adverse fetal outcomes.

Results: 2116 HIV-uninfected pregnant women age 18 to 38 years, received either IIV3 or placebo given during pregnancy at an estimated gestation of 20 - 36 weeks. There were 2036 known fetal outcomes including 6 miscarriages and 23 stillbirths from the mothers in the study who had been vaccinated >14 days prior to the outcome. There was no significant association between influenza vaccine exposure and any fetal outcome of stillbirth, prematurity, SGA or LBW. The mean GA at birth was significantly higher in the placebo-group (p =39.1) compared to the IIV3-group (v =38.9; P =0.0496; Wilcoxon Test P = 0.042), with a concomitant 40g difference in birth weight (v =3035g vs. p =3075; P =0.077; Wilcoxon Test P =0.213). There were no statistically significant findings of VE  and differences between incidence rates for any of the other fetal outcome measures. Neither was an association demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (N = 1832) with the mean birth weight difference by mother’s intervention status approaching significance (v =3047g, p =3089g; P =0.072), the rate of LBW infants was however similar in the two groups (11.6% in the IIV3-group vs. 9.8% in the placebo-group; P =0.24). Of 30 infants born to the mothers who contracted influenza prior to delivery, no worse fetal outcomes were observed, except for lower rate of near term births (IRR = 0.61; P = 0.006).

Conclusion: There was no evidence of a beneficial effect of IIV3, or negative effect of seasonal influenza infection during pregnancy on fetal outcomes.

Eric A. F. Simões, MB; BS, DCH, MD1,2,3, Claire Cutland, MD4, Phyllis Carosone-Link, MSPH5, Andrea Hugo, MD2, Stephanie Jones, MD2, Richard Madimabe, B Tech2, Justin Ortiz, MD, MS6, Kathleen Neuzil, MD, MPH, FIDSA6, Keith Klugman, MD, PhD, FIDSA2, Marta Nunes, PhD2, Shabir Madhi, MD, PhD7 and MatFlu Team, (1)University of Colorado School of Medicine, Aurora, CO, (2)Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa, (3)Department of Epidemiology and Center for Global Health, Colorado School of Public Health, Aurora, CO, (4)DST/NRF Vaccine Preventable Diseases, University of the Witwatersrand, South Africa, Johannesburg, South Africa, (5)Childrens Hospital Colorado, Aurora, CO, (6)PATH, Seattle, WA, (7)Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Bertsham, South Africa

Disclosures:

E. A. F. Simões, Bill and Melinda Gates Foundation: Grant Investigator , Grant recipient

C. Cutland, Bill and Melinda Gates Foundation: Grant Investigator , Research support

P. Carosone-Link, Bill and Melinda Gates Foundation: Grant Investigator , Research support

A. Hugo, Bill and Melinda Gates Foundation: Grant Investigator , Research support

S. Jones, Bill and Melinda Gates Foundation: Grant Investigator , Research support

R. Madimabe, Bill and Melinda Gates Foundation: Grant Investigator , Research support

J. Ortiz, None

K. Neuzil, Bill and Melinda Gates Foundation: Grant Investigator , Research support

K. Klugman, Bill and Melinda Gates Foundation: Grant Investigator , Research support

M. Nunes, Bill and Melinda Gates Foundation: Grant Investigator , Research support

S. Madhi, Bill and Melinda Gates Foundation: Grant Investigator , Grant recipient and Research support

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