Research Obstetrics| Volume 198, ISSUE 2, P178.e1-178.e7, February 2008

Acetaminophen use during pregnancy: effects on risk for congenital abnormalities


      We evaluated if acetaminophen, one of the most frequently used drugs among pregnant women is associated with an increased prevalence of congenital abnormalities.

      Study Design

      We selected 88,142 pregnant women and their liveborn singletons from the Danish National Birth Cohort who had information on acetaminophen use during the first trimester of pregnancy. We used the National Hospital Registry to identify 3784 (4.3%) children from the cohort diagnosed with 5847 congenital abnormalities.


      Children exposed to acetaminophen during the first trimester of pregnancy (n = 26,424) did not have an increased prevalence of congenital abnormalities (hazard ratio = 1.01, 0.93-1.08) compared with nonexposed children (n = 61,718). No association was found between congenital abnormalities and duration of use during the first trimester. Increased prevalence was not observed for specific abnormalities, except for “medial cysts, fistula, sinus” (congenital abnormalities of the ear, face, and neck, ICD-10 code Q18.8, n = 43) with an adjusted hazard ratio of 2.15 (1.17-3.95).


      Acetaminophen is not associated with an increased prevalence of congenital abnormalities overall or with any specific group of major abnormalities.

      Key words

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        • Headley J.
        • Northstone K.
        • Simmones H.
        • Golding J.
        Medication use during pregnancy: data from the Avon Longitudinal Study of Parents and Children.
        Eur J Clin Pharmacol. 2004; 60: 355-361
        • Werler M.M.
        • Mitchell A.A.
        • Hernandez-Diaz S.
        • Honein M.A.
        Use of over-the-counter medications during pregnancy.
        Am J Obstet Gynecol. 2005; 193: 771-777
        • Rayburn W.
        • Shukla U.
        • Stetnson P.
        • Piehl E.
        Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women.
        Am J Obstet Gynecol. 1986; 155: 1353-1356
        • Rathmell J.P.
        • Viscomi C.A.
        • Ashburn M.A.
        Management of nonobstetric pain during pregnancy and lactation.
        Anesth Analg. 1997; 85: 1074-1087
        • Burdan F.
        • Siezieniewska Z.
        • Kis G.
        • Blicharski T.
        Embryotoxicity of acetaminophen (paracetamol) in experimental in vivo model.
        Ann Univ Marie Curie Sklodowska [Med]. 2001; 56: 89-94
        • Burdan F.
        Intrauterine growth retardation and lack of teratogenic effects of prenatal exposure to combination of paracetamol and caffeine in Wistar in rats.
        Reprod Toxicol. 2003; 17: 51-58
        • Friedman J.M.
        • Little B.B.
        • Brent R.L.
        • Cordero J.F.
        • Hanson J.W.
        • Shepard T.H.
        Potential human teratogenicity of frequently prescribed drugs.
        Obstet Gynecol. 1990; 75: 594-599
        • Aselton P.
        • Jick H.
        • Milunsky A.
        • Hunter J.R.
        • Stergachis A.
        First-trimester drug use and congenital disorders.
        Obstet Gynecol. 1985; 65: 451-455
        • Briggs G.G.
        • Freeman R.K.
        • Yaffe S.J.
        Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk.
        6th ed. Lippincott Williams & Wilkins, Philadelpia, PA2002
        • Thulstrup A.M.
        • Sorensen H.T.
        • Nielsen G.L.
        • et al.
        Fetal growth and adverse birth outcomes in women receiving prescriptions fro acetaminophen during pregnancy.
        Am J Perinatol. 1999; 16: 321-326
        • Olesen C.
        • Sondergaard C.
        • Thrane N.
        • Nielsen G.L.
        • de Jong-van den Berg
        • Olsen J.
        Do pregnant women report use of dispensed medications?.
        Epidemiology. 2001; 12: 497-501
        • Heinonen O.P.
        • Slone P.
        • Shapiro S.
        Birth defects and drugs in pregnancy.
        John Wright-PSG, Littleton, MA1987
        • Czeizel A.E.
        • Dudás I.
        • Puhó E.
        Short-term paracetamol therapy during pregnancy and a lower rate of preterm birth.
        Paediat Perinatal Epidemiol. 2005; 19: 106-111
        • Werler M.M.
        • Mitchell A.A.
        • Shapiro S.
        First trimester maternal medication use in relation to gastroschisis.
        Teratology. 1992; 45: 361-367
        • Werler M.M.
        • Sheehan J.E.
        • Mitchell A.A.
        Maternal medication use and risks of gastroschisis and small intestinal atresia.
        Am J Epidemiol. 2002; 155: 26-31
        • Werler M.M.
        • Louik C.
        • Mitchell A.A.
        Epidemiologic analysis of maternal factors and amniotic band defects.
        Birth Defects Res A Clin Mol Teratol. 2004; 67: 68-72
        • Cleves M.A.
        • Savell Jr, V.H.
        • Raj S.
        • et al.
        Maternal use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and muscular ventricular septal defects.
        Birth Defects Res A Clin Mol Teratol. 2004; 70: 107-113
        • Nohr E.A.
        • Frydenberg M.
        • Henriksen T.B.
        • Olsen J.
        Does low participation in cohort studies induce bias?.
        Epidemiology. 2001; 17: 413-418
        • Olsen J.
        • Melbye M.
        • Olsen S.F.
        • et al.
        The Danish National Birth Cohort—its background, structure and aim.
        Scand J Public Health. 2001; 29: 300-307
        • Acs N.
        • Bánhidy F.
        • Puhó E.
        • Czeizel A.E.
        Maternal influenza during pregnancy and risk of congenital abnormalities in offspring.
        Birth Defects Res Part A. 2005; 73: 989-996
        • Signorello L.B.
        • McLaughlin J.K.
        • Lipworth L.
        • Friis S.
        • Sorensen H.T.
        • Blot W.J.
        Confounding by indication in epidemiologic studies of commonly used analgesics.
        Am J Ther. 2002; 9: 199-205
        • Bánhidy F.
        • Lowry R.B.
        • Czeizel A.E.
        Risk and benefit of drug use in pregnancy.
        Int J Med Sci. 2005; 2: 100-106
        • Czeizel A.E.
        First 25 years of Hungarian Congenital Abnormalities Registry.
        Teratology. 1997; 55: 299-305
      1. Department of Health. New York State. Statistical summary of children born in 1998-2001 and diagnosed through 2003. Congenital Malformations Registry—Summary Report.
        (Accessed August 8, 2006)
        • McElhatton P.R.
        • Sullivan F.M.
        • Volans G.N.
        Paracetamol overdose in pegnancy analysis of the outcomes of 300 vases referred to the Teratology Information Service.
        Reprod Toxicol. 1997; 11: 85-94