The Association of H1N1 Pandemic Influenza with Congenital Anomaly Prevalence in Europe: An Ecological Time Series Study.
BACKGROUND
In the context of the European Surveillance of Congenital Anomalies (EUROCAT) surveillance response to the 2009 influenza pandemic, we sought to establish whether there was a detectable increase of congenital anomaly prevalence among pregnancies exposed to influenza seasons in general, and whether any increase was greater during the 2009 pandemic than during other seasons.


METHODS
We performed an ecologic time series analysis based on 26,967 pregnancies with nonchromosomal congenital anomaly conceived from January 2007 to March 2011, reported by 15 EUROCAT registries. Analysis was performed for EUROCAT-defined anomaly subgroups, divided by whether there was a prior hypothesis of association with influenza. Influenza season exposure was based on World Health Organization data. Prevalence rate ratios were calculated comparing pregnancies exposed to influenza season during the congenital anomaly-specific critical period for embryo-fetal development to nonexposed pregnancies.


RESULTS
There was no evidence for an increased overall prevalence of congenital anomalies among pregnancies exposed to influenza season. We detected an increased prevalence of ventricular septal defect and tricuspid atresia and stenosis during pandemic influenza season 2009, but not during 2007-2011 influenza seasons. For congenital anomalies, where there was no prior hypothesis, the prevalence of tetralogy of Fallot was strongly reduced during influenza seasons.


CONCLUSIONS
Our data do not suggest an overall association of pandemic or seasonal influenza with congenital anomaly prevalence. One interpretation is that apparent influenza effects found in previous individual-based studies were confounded by or interacting with other risk factors. The associations of heart anomalies with pandemic influenza could be strain specific.
From the aInstitute of Nursing Research/School of Nursing, University of Ulster, Newtownabbey, United Kingdom; bDivision of Medical Genetics, Lausanne, Switzerland; cPublic Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, CIBER Epidemiología y Salud Pública-CIBERESP, Madrid, Spain; dUnit of Epidemiology, Institute of Clinical Physiology, Pisa, Italy; eDepartment of Paediatrics, Hospital Lillebaelt, Kolding, Denmark; fINSERM U953, Paris, France; gProvinciaal Instituut voor Hygiene, Antwerp, Belgium; hIMER Registry-Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy; iUniversity Medical Center of the Johannes Gutenberg University, Mainz, Germany; jInstitute of Health & Society, Newcastle University, Newcastle-upon-Tyne, United Kingdom; kNational Perinatal Epidemiology Unit, University of Oxford, Oxford, United Kingdom; lInstitut de Pathologie et de Génétique, Charleroi, Belgium; mDepartment of Genetics, University Medical Center Groningen, University of Groningen, Eurocat, Groningen, The Netherlands; nWessex Clinical Genetics Service, Princess Anne Hospital, Southampton, United Kingdom; oSchool of Clinical Sciences, University of Bristol, Bristol, United Kingdom; pOMNI-Net for Children, Rivne Medical Diagnostic Center, Rivne, Ukraine; qDivision of Pharmacy, Department of Pharmacoepidemiology and Pharmacoeconomics, University of Groningen, Groningen, The Netherlands; and rCentre for Environmental and Preventive Medicine, Queen Mary University of London, London, United Kingdom.
Johannes Michiel
JM
Luteijn
Marie-Claude
MC
Addor
Larraitz
L
Arriola
Fabrizio
F
Bianchi
Ester
E
Garne
Babak
B
Khoshnood
Vera
V
Nelen
Amanda
A
Neville
Annette
A
Queisser-Luft
Judith
J
Rankin
Catherine
C
Rounding
Christine
C
Verellen-Dumoulin
Hermien
H
de Walle
Diana
D
Wellesley
Ben
B
Wreyford
Lyubov
L
Yevtushok
Lolkje
L
de Jong-van den Berg
Joan
J
Morris
Helen
H
Dolk
D000013:Congenital Abnormalities / Q000453:epidemiology*; D015615:Cystic Adenomatoid Malformation of Lung, Congenital / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006345:Heart Septal Defects, Ventricular / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology; D009436:Neural Tube Defects / Q000453:epidemiology; D058873:Pandemics; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology*; D015995:Prevalence; D012042:Registries; D013771:Tetralogy of Fallot / Q000453:epidemiology; D018785:Tricuspid Atresia / Q000453:epidemiology; D014264:Tricuspid Valve Stenosis / Q000453:epidemiology