Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum



      The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors.

      Study design

      This is a case–control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test.


      Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome.


      Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Jiang H.G.
        • Elixhauser A.
        • Nicholas J.
        • SteinerC
        • Reyes C.
        • Brierman AS
        Care of women in US hospitals, 2000: HCUP fact book no. 3, no. 02-0044.
        Agency for Healthcare Research and Quality, Rockville, MD2002
        • Verberg M.F.
        • Gillott D.J.
        • Al-Fardan N.
        • Grudzinskas J.G.
        Hyperemesis gravidarum, a literature review.
        Hum Reprod Update. 2005; 11: 527-539
        • Källén B.
        Hyperemesis during pregnancy and delivery outcome: a registry study.
        Eur J Obstet Gynecol Reprod Biol. 1987; 26: 291-302
        • Zhang J.
        • Cai W.W.
        Severe vomiting during pregnancy: antenatal correlates and fetal outcomes.
        Epidemiology. 1991; 2: 454-457
        • Chiossi G.
        • Neri I.
        • Cavazutti M.
        • Basso G.
        • Fucchinetti F.
        Hyperemesis gravidarum complicated by Wernicke's encephalopathy: background, case report and review of the literature.
        Obstet Gynecol Surv. 2006; 61: 255-268
        • Bailit J.L.
        Hyperemesis gravidarum: epidemiologic findings from a large cohort.
        Am J Obstet Gynecol. 2005; 193: 811-814
        • Fairweather D.V.I.
        Nausea and vomiting in pregnancy.
        Am J Obstet Gynecol. 1968; 102: 135-175
        • Goodwin T.M.
        Hyperemesis gravidarum.
        Clin Obstet Gynecol. 1998; 41: 597-605
        • Fejzo M.S.
        • Poursharif B.
        • Korst L.M.
        • et al.
        Symptoms and pregnancy outcomes associated with extreme weight loss among women with HG.
        J Womens Health. 2009; 18: 1981-1987
        • van Oppenraaij R.H.
        • Jauniaux E.
        • Christiansen O.B.
        • et al.
        Predicting adverse obstetric outcome after early pregnancy events and complications: a review.
        Hum Reprod Update. 2009; 15: 409-421
        • Veenendaal M.V.
        • van Abeelen A.F.
        • Painter R.C.
        • van der Post J.A.
        • Roseboom T.J.
        Consequences of hyperemesis gravidarum for offspring: a systematic review and meta-analysis.
        BJOG. 2011; 118: 1302-1313
        • Folk J.J.
        • Leslie-Brown H.F.
        • Nosovitch J.T.
        • Silverman R.K.
        • Aubry R.H.
        Hyperemesis gravidarum: outcomes and complications with and without total parenteral nutrition.
        J Reprod Med. 2004; 49: 497-502
        • Paranyuk Y.
        • Levine G.
        • Figueroa R.
        Candida septicemia in a pregnant woman with hyperemesis receiving parenteral nutrition.
        Obstet Gynecol. 2006; 107: 535-537
        • Roseboom T.J.
        • Ravelli A.C.
        • van der Post J.A.
        • Painter R.C.
        Maternal characteristics largely explain poor pregnancy outcome after hyperemesis gravidarum.
        Eur J Obstet Gynecol Reprod Biol. 2011; 156: 56-59
        • Spiegler J.
        • Stichtenoth G.
        • Weichert J.
        • et al.
        Pregnancy risk factors for very premature delivery: what role do hypertension, obesity and diabetes play?.
        Arch Gynecol Obstet. 2013; ([Epub ahead of print])
        • Micali N.
        • De Stavola B.
        • dos-Santos-Silva I.
        • et al.
        Perinatal outcomes and gestational weight gain in women with eating disorders: a population-based cohort study.
        BJOG. 2012; 119: 1493-1502
        • Goodwin T.M.
        • Poursharif B.
        • Korst L.M.
        • MacGibbon K.
        • Fejzo M.S.
        Secular trends in the treatment of hyperemesis gravidarum.
        Am J Perinatol. 2008; 25: 141-147
        • Mazzotta P.
        • Magee L.A.
        A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy.
        Drugs. 2000; 59: 781-800
        • Bártfai Z.
        • Kocsis J.
        • Puhó E.H.
        • Czeizel A.E.
        A population-based case-control study of promethazine use during pregnancy.
        Reprod Toxicol. 2008; 25: 276-285
        • Källén B.
        Use of antihistamine drugs in early pregnancy and delivery outcome.
        J Matern Fetal Neonatal Med. 2002; 11: 146-152
        • Czeizel A.E.
        • Puhó E.
        Association between severe nausea and vomiting in pregnancy and lower rate of preterm births.
        Paediatr Perinat Epidemiol. 2004; 18: 253-259