title: Neuraminidase inhibitors during pregnancy and risk of adverse neonatal outcomes and congenital malformations: population based European register study.
abstract: ObjectiveTo evaluate the possible effects of exposure to neuraminidase inhibitors during embryo-fetal life with respect to adverse neonatal outcomes and congenital malformations.DesignPopulation based multinational observational cohort study and meta-analysis.SettingNational registers covering information on maternal healthcare, births, and prescriptions in Denmark, Norway, and Sweden and the EFEMERIS database from the Haute-Garonne district in France.ParticipantsAll women together with their singleton infants born between 1 January 2008 and 31 December 2010. Only infants born at 154 days of gestation or later were included. Infants were defined as exposed if the women filled a prescription during pregnancy for either of the two neuraminidase inhibitors oseltamivir or zanamivir.Main outcomesLow birth weight, low Apgar score, preterm birth, small for gestational age birth, stillbirth, neonatal mortality, neonatal morbidity, and congenital malformations. Crude and adjusted hazard ratios of preterm birth were estimated using Cox regression models. Crude and adjusted odds ratios for other outcomes were estimated by logistic regression models.ResultsThe study included 5824 (0.8%) exposed women and their infants and 692 232 who were not exposed. Exposure to neuraminidase inhibitors in utero was not associated with increased risks of any of the investigated neonatal outcomes, including low birth weight (adjusted odds ratio 0.77, 95% confidence interval 0.65 to 0.91), low Apgar score (adjusted odds ratio 0.87, 0.67 to 1.14), preterm birth (adjusted hazard ratio 0.97, 0.86 to 1.10), small for gestational age birth (adjusted odds ratio 0.72, 0.59 to 0.87), stillbirth (adjusted odds ratio 0.81, 0.51 to 1.30), neonatal mortality (adjusted odds ratio 1.13, 0.56 to 2.28), and neonatal morbidity (adjusted odds ratio 0.92, 0.86 to 1.00). No increased risk of congenital malformations overall associated with maternal exposure was observed during the first trimester (adjusted odds ratio 1.06, 0.77 to 1.48). Similarly, no significantly increased risks of any of the outcomes were observed in an analysis restricted to oseltamivir alone.ConclusionsThis large multinational register study found no increased risks of adverse neonatal outcomes or congenital malformations associated with exposure to neuraminidase inhibitors during embryo-fetal life. The results support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes.
authors.affiliation: Department of Medicine, Centre for Pharmacoepidemiology, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden.|Department of Obstetrics and Gynecology, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Graner
authors.affiliation: Department of Medicine, Centre for Pharmacoepidemiology, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
authors.forename: Tobias
authors.initials: T
authors.lastname: Svensson
authors.affiliation: Service de Pharmacologie Médicale, CHU Toulouse, Université Toulouse III, UMR INSERM, FR-1027 Toulouse, France.
authors.forename: Anna-Belle
authors.initials: AB
authors.lastname: Beau
authors.affiliation: Service de Pharmacologie Médicale, CHU Toulouse, Université Toulouse III, UMR INSERM, FR-1027 Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Damase-Michel
authors.affiliation: Division of Mental and Physical Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, NO-0403, Oslo, Norway.|Department of Global Public Health and Primary Care, University of Bergen, NO-5020 Bergen, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Engeland
authors.affiliation: Division of Mental and Physical Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, NO-0403, Oslo, Norway.
authors.forename: Kari
authors.initials: K
authors.lastname: Furu
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300, Copenhagen S, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
authors.affiliation: Division of Mental and Physical Health, Norwegian Institute of Public Health, P.O. Box 4404, Nydalen, NO-0403, Oslo, Norway.
authors.forename: Siri Eldevik
authors.initials: SE
authors.lastname: Håberg
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300, Copenhagen S, Denmark.
authors.forename: Ditte
authors.initials: D
authors.lastname: Mølgaard-Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300, Copenhagen S, Denmark.|Clinical epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.affiliation: Department of Medicine, Centre for Pharmacoepidemiology, Karolinska Institutet, Karolinska University Hospital, SE-17176 Stockholm, Sweden.
authors.forename: Helle
authors.initials: H
authors.lastname: Kieler
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D015897:Comorbidity; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015201:Meta-Analysis as Topic; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D012042:Registries; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D009439:Neuraminidase