paa Madhi 2014.

Methods	Randomised controlled trial carried out on pregnant women to assess the effectiveness of trivalent inactivated influenza vaccine administration during pregnancy against confirmed influenza in women and their newborn. The study was carried out during 2 subsequent epidemic seasons (2011 and 2012).
Participants	Pregnant women aged between 18 and 38 years and having an estimated gestation between 20 and 36 weeks who tested negative for HIV were recruited at 4 antenatal clinics of Soweto, South Africa, during 2 consecutive epidemic seasons (March to August 2011 and March to July 2012). In all, 2116 women entered the study: 1062 were allocated to receive vaccine, 1054 to placebo. In addition, 1026 infants born from vaccinated mothers and 1023 infants born from placebo recipients were enrolled.
Interventions	Women enrolled in the study were randomised 1:1 using a computer‐generated assignment and a block size of 30 and allocated to 1 of the following treatments: Trivalent inactivated influenza vaccine (Vaxigrip, lot number G05831 in 2011 and H7221‐2 in 2012; Sanofi Pasteur) containing 15 μg each of A/California/7/2009 (A/(H1N1)pdm09), A/Victoria/210/2009 (A/H3N2), and a B/Brisbane/60/2008–like virus (B/Victoria), as recommended by WHO for the Southern Hemisphere in 2011 and 2012 Placebo consisting of sterile 0.9% saline solution Both preparations were administered by study staff in the deltoid muscle in a 0.5 mL dose and were macroscopically indistinguishable.
Outcomes	Cases of ILI were identified through active surveillance. The following criteria were used to identify cases among mother and infants respectively: ILI (mothers): fever ≥ 38 °C on oral measurement or history of chills, rigors, or feeling feverish; AND presence of cough or sore throat or pharyngitis; OR presence of myalgia, arthralgia, or headache; OR presence of dyspnoea, breathing difficulty, or chest pain when breathing. ILI (infants): axillary temperature ≥ 37.8 °C or mother’s perception that the infant was feverish, or both, without evidence of a non‐respiratory localised source, coupled with at least 1 sign or symptom of acute respiratory infection within the past 72 hours; OR at least 2 signs and/or symptoms of acute respiratory illness within the past 72 hours including: respiratory rate of ≥ 60 and ≥ 50 breaths per minute in infant 0 to 2 months and 2 to 6 months of age, respectively; difficulty breathing reported by the mother, cough, wheezing, runny or congested nose, cyanosis or oxygen saturation < 90% on room air, chest wall in‐drawing, grunting on expiration, and pus draining from either ear. Influenza: women and infants with ILI, as well as those presenting or hospitalised at antenatal clinics for any respiratory illness, who underwent PCR test with a positive result for influenza viruses. Events occurring within the timespans of 24 weeks' postpartum (for women) and the 24th week of age (for infants) have been considered for analysis. Local and systemic reactions recorded on diary cards during the first week following immunisation
Notes	Funding source ‐ industry Supported by grants from the Bill and Melinda Gates Foundation (OPP1002747), the National Institutes of Health, National Center for Advancing Translational Sciences Colorado Clinical and Translational Sciences Institute (UL1 TR000154, for REDCap), the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation in Vaccine‐Preventable Diseases, and the Respiratory and Meningeal Pathogens Research Unit of the Medical Research Council.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation lists, in blocks of 30 (15 IIV3, 15 placebo) were generated with assignment of a 4‐digit study number being done in sequence of enrolment (SAS 9.1, SAS Institute Inc., Cary, NC, USA).
Allocation concealment (selection bias)	Low risk	Block size of 30 were allocated consecutively to the enrolling sites, after which the randomisation forms for that block were provided to the site in sealed, consecutively numbered envelopes with the pre‐printed study number and the alphabetical code for vaccine or placebo in the envelope.
Blinding (performance bias and detection bias) All outcomes	Low risk	Both administered preparations were macroscopically indistinguishable. With the exception of the statistician and the pharmacist, study personnel and study participants were unaware of the group assignments.
Incomplete outcome data (attrition bias) All outcomes	Low risk	None
Summary assessment	Low risk	Low risk of bias