Maternal influenza and birth outcomes: systematic review of comparative studies.
BACKGROUND
Although pregnant women are considered at high risk for severe influenza disease, comparative studies of maternal influenza and birth outcomes have not been comprehensively summarised.


OBJECTIVE
To review comparative studies evaluating maternal influenza disease and birth outcomes.


METHODS
We searched bibliographic databases from inception to December 2014.


METHODS
Studies of preterm birth, small-for-gestational-age (SGA) birth or fetal death, comparing women with and without clinical influenza illness or laboratory-confirmed influenza infection during pregnancy.


METHODS
Two reviewers independently abstracted data and assessed study quality.


RESULTS
Heterogeneity across 16 studies reporting preterm birth precluded meta-analysis. In a subgroup of the highest-quality studies, two reported significantly increased preterm birth (risk ratios (RR) from 2.4 to 4.0) following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild-to-moderate pH1N1 or seasonal influenza found no association. Five studies of SGA birth showed no discernible patterns with respect to influenza disease severity (pooled odds ratio 1.24; 95% CI 0.96-1.59). Two fetal death studies were of sufficient quality and size to permit meaningful interpretation. Both reported an increased risk of fetal death following maternal pH1N1 disease (RR 1.9 for mild-to-moderate disease and 4.2 for severe disease).


CONCLUSIONS
Comparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association.


CONCLUSIONS
Comparative studies are limited in quality but suggest severe pandemic H1N1 influenza increases preterm birth.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.|Better Outcomes Registry & Network (BORN), CHEO Research Institute, Ottawa, ON, Canada.
D B
DB
Fell
Department of Epidemiology, Brown University, Providence, RI, USA.|Department of Obstetrics and Gynecology, Brown University, Providence, RI, USA.
D A
DA
Savitz
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada.|Department of Pediatrics, McGill University Faculty of Medicine, Montreal, QC, Canada.
M S
MS
Kramer
Agence de Médecine Préventive, Paris, France.
B D
BD
Gessner
Independent Consultant, Tel Aviv, Israel.
M A
MA
Katz
National Perinatal Epidemiology Unit, University of Oxford, Oxford, UK.
M
M
Knight
Queen Mary University of London, London, UK.
J M
JM
Luteijn
Vaccinology and Immunology Research Trials Unit, Women's and Children's Hospital, North Adelaide, SA, Australia.|School of Medicine, University of Adelaide, North Adelaide, SA, Australia.|Robinson Research Institute, University of Adelaide, North Adelaide, SA, Australia.
H
H
Marshall
PATH, Seattle, WA, USA.
N
N
Bhat
Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA.|Global Alliance to Prevent Prematurity and Stillbirth, Seattle Children's, Seattle, WA, USA.
M G
MG
Gravett
Independent Consultant, Ottawa, ON, Canada.
B
B
Skidmore
Initiative for Vaccine Research, World Health Organization, Geneva, Switzerland.
J R
JR
Ortiz
D000328:Adult; D005260:Female; D005313:Fetal Death / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D053118:Influenza A Virus, H1N1 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000150:complications / Q000453:epidemiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology* / Q000821:virology; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
Fetal death; influenza; pregnancy; preterm birth; small-for-gestational-age birth; systematic review