FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 335:1010-1015 October 3, 1996 Number 14 Next

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Although fluoxetine is the most frequently prescribed antidepressant drug in the United States, its safety in pregnant women has not been established.

Methods From 1989 through 1995, we prospectively identified 228 pregnant women taking fluoxetine. We compared the outcomes of their pregnancies with those of 254 women identified in a similar manner who were not taking fluoxetine.

Results The rate of spontaneous pregnancy loss did not differ significantly between the women treated with fluoxetine and the control women (10.5 percent and 9.1 percent, respectively), nor was the rate of major structural anomalies significantly different (5.5 percent vs. 4.0 percent). Among the 97 infants exposed to fluoxetine who were evaluated for minor anomalies, the incidence of three or more minor anomalies was significantly higher than among 153 similarly examined control infants (15.5 percent vs. 6.5 percent, P = 0.03). As compared with the 101 infants exposed to fluoxetine only during the first and second trimesters, the 73 infants exposed during the third trimester had higher rates of premature delivery (relative risk, 4.8; 95 percent confidence interval, 1.1 to 20.8), admission to special-care nurseries (relative risk, 2.6; 95 percent confidence interval, 1.1 to 6.9), and poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding, and jitteriness (relative risk, 8.7; 95 percent confidence interval, 2.9 to 26.6). Birth weight was also lower and birth length shorter in infants exposed to fluoxetine late in gestation.

Conclusions Women who take fluoxetine during pregnancy do not have an increased risk of spontaneous pregnancy loss or major fetal anomalies, but women who take fluoxetine in the third trimester are at increased risk for perinatal complications.

Source Information

From the Department of Pediatrics, Division of Dysmorphology and Teratology, University of California–San Diego, La Jolla.

Address reprint requests to Dr. Jones at the Department of Pediatrics #8446, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103.

Full Text of this Article

Related Letters:

Birth Outcomes in Pregnant Women Taking Fluoxetine
Cohen L. S., Rosenbaum J. F., Goldstein D. J., Sundell K. L., Corbin L. A., Jones K. L., Johnson K. A., Chambers C. D.
Extract | Full Text  
N Engl J Med 1997; 336:872-873, Mar 20, 1997. Correspondence

This article has been cited by other articles:

• Wisner, K. L., Sit, D. K.Y., Hanusa, B. H., Moses-Kolko, E. L., Bogen, D. L., Hunker, D. F., Perel, J. M., Jones-Ivy, S., Bodnar, L. M., Singer, L. T. (2009). Major Depression and Antidepressant Treatment: Impact on Pregnancy and Neonatal Outcomes. Am. J. Psychiatry 166: 557-566 [Abstract] [Full Text]  
• Toh, S., Mitchell, A. A., Louik, C., Werler, M. M., Chambers, C. D., Hernandez-Diaz, S. (2009). Selective Serotonin Reuptake Inhibitor Use and Risk of Gestational Hypertension. Am. J. Psychiatry 166: 320-328 [Abstract] [Full Text]  
• Wichman, C. L., Moore, K. M., Lang, T. R., Sauver, J. L. St., Heise, R. H. Jr, Watson, W. J. (2009). Congenital Heart Disease Associated With Selective Serotonin Reuptake Inhibitor Use During Pregnancy. Mayo Clin Proc. 84: 23-27 [Abstract] [Full Text]  
• Rajkumar, A. P., Jacob, K. S. (2008). Are antidepressants safe during pregnancy?. Br. J. Psychiatry 193: 508-508 [Full Text]  
• Berard, A., Ramos, E. (2008). Authors' reply:. Br. J. Psychiatry 193: 508-509 [Full Text]  
• Conlon, O., Lynch, J. (2008). Maternal depression: risk factors and treatment options during pregnancy. The Obstetrician and Gynaecologist 10: 151-155 [Abstract] [Full Text]  
• Rich-Edwards, J. W., Mohllajee, A. P., Kleinman, K., Hacker, M. R., Majzoub, J., Wright, R. J., Gillman, M. W. (2008). Elevated Midpregnancy Corticotropin-Releasing Hormone Is Associated with Prenatal, But Not Postpartum, Maternal Depression. J. Clin. Endocrinol. Metab. 93: 1946-1951 [Abstract] [Full Text]  
• Oberlander, T. F., Warburton, W., Misri, S., Aghajanian, J., Hertzman, C. (2008). Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study. Br. J. Psychiatry 192: 338-343 [Abstract] [Full Text]  
• Ramos, E., St-Andre, M., Rey, E., Oraichi, D., Berard, A. (2008). Duration of antidepressant use during pregnancy and risk of major congenital malformations. Br. J. Psychiatry 192: 344-350 [Abstract] [Full Text]  
• Fornaro, E., Li, D., Pan, J., Belik, J. (2007). Prenatal Exposure to Fluoxetine Induces Fetal Pulmonary Hypertension in the Rat. Am. J. Respir. Crit. Care Med. 176: 1035-1040 [Abstract] [Full Text]  
• Suri, R., Altshuler, L., Hellemann, G., Burt, V. K., Aquino, A., Mintz, J. (2007). Effects of Antenatal Depression and Antidepressant Treatment on Gestational Age at Birth and Risk of Preterm Birth. Am. J. Psychiatry 164: 1206-1213 [Abstract] [Full Text]  
• (2007). Follow-Up on Antidepressants During Pregnancy: An Exchange of Views. JWatch Women's Health 2007: 6-6 [Full Text]  
• Louik, C., Lin, A. E., Werler, M. M., Hernandez-Diaz, S., Mitchell, A. A. (2007). First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of Birth Defects. NEJM 356: 2675-2683 [Abstract] [Full Text]  
• Alwan, S., Reefhuis, J., Rasmussen, S. A., Olney, R. S., Friedman, J. M., the National Birth Defects Prevention Study, (2007). Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. NEJM 356: 2684-2692 [Abstract] [Full Text]  
• Looper, K. J. (2007). Potential Medical and Surgical Complications of Serotonergic Antidepressant Medications. Psychosomatics 48: 1-9 [Abstract] [Full Text]  
• Ferreira, E., Carceller, A. M., Agogue, C., Martin, B. Z., St-Andre, M., Francoeur, D., Berard, A. (2007). Effects of Selective Serotonin Reuptake Inhibitors and Venlafaxine During Pregnancy in Term and Preterm Neonates. Pediatrics 119: 52-59 [Abstract] [Full Text]  
• Oberlander, T. F., Warburton, W., Misri, S., Aghajanian, J., Hertzman, C. (2006). Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data.. Arch Gen Psychiatry 63: 898-906 [Abstract] [Full Text]  
• Bodnar, L. M., Sunder, K. R., Wisner, K. L. (2006). Treatment With Selective Serotonin Reuptake Inhibitors During Pregnancy: Deceleration of Weight Gain Because of Depression or Drug?. Am. J. Psychiatry 163: 986-991 [Full Text]  
• Aldous, M. B. (2006). SSRI Withdrawal Syndrome in Term Newborns. AAP Grand Rounds 15: 72-73 [Full Text]  
• Chambers, C. D., Hernandez-Diaz, S., Van Marter, L. J., Werler, M. M., Louik, C., Jones, K. L., Mitchell, A. A. (2006). Selective Serotonin-Reuptake Inhibitors and Risk of Persistent Pulmonary Hypertension of the Newborn. NEJM 354: 579-587 [Abstract] [Full Text]  
• Mills, J. L. (2006). Depressing Observations on the Use of Selective Serotonin-Reuptake Inhibitors during Pregnancy. NEJM 354: 636-638 [Full Text]  
• Cohen, L. S., Altshuler, L. L., Harlow, B. L., Nonacs, R., Newport, D. J., Viguera, A. C., Suri, R., Burt, V. K., Hendrick, V., Reminick, A. M., Loughead, A., Vitonis, A. F., Stowe, Z. N. (2006). Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment. JAMA 295: 499-507 [Abstract] [Full Text]  
• Levinson-Castiel, R., Merlob, P., Linder, N., Sirota, L., Klinger, G. (2006). Neonatal Abstinence Syndrome After In Utero Exposure to Selective Serotonin Reuptake Inhibitors in Term Infants. Arch Pediatr Adolesc Med 160: 173-176 [Abstract] [Full Text]  
• Haddad, P. M., Pal, B. R., Clarke, P., Wieck, A., Sridhiran, S. (2005). Neonatal symptoms following maternal paroxetine treatment: Serotonin toxicity or paroxetine discontinuation syndrome?. J Psychopharmacol 19: 554-557 [Abstract]  
• Mornson, J. L., Rurak, D. W., Chien, C., Kennaway, D. J., Gruber, N., McMillen, I. C., Riggs, K. W. (2005). Maternal Fluoxetine Infusion Does Not Alter Fetal Endocrine and Biophysical Circadian Rhythms in Pregnant Sheep. Reproductive Sciences 12: 356-364 [Abstract]  
• Koren, G., Matsui, D., Einarson, A., Knoppert, D., Steiner, M. (2005). Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates?. CMAJ 172: 1457-1459 [Full Text]  
• Moses-Kolko, E. L., Bogen, D., Perel, J., Bregar, A., Uhl, K., Levin, B., Wisner, K. L. (2005). Neonatal Signs After Late In Utero Exposure to Serotonin Reuptake Inhibitors: Literature Review and Implications for Clinical Applications. JAMA 293: 2372-2383 [Abstract] [Full Text]  
• Hemels, M. E., Einarson, A., Koren, G., Lanctot, K. L, Einarson, T. R (2005). Antidepressant Use During Pregnancy and the Rates of Spontaneous Abortions: A Meta-Analysis. The Annals of Pharmacotherapy 39: 803-809 [Abstract] [Full Text]  
• Vanhaesebrouck, P., De Bock, F., Zecic, A., De Praeter, C., Smets, K., De Coen, K., Goossens, L. (2005). Phototherapy-Mediated Syndrome of Inappropriate Secretion of Antidiuretic Hormone in an In Utero Selective Serotonin Reuptake Inhibitor-Exposed Newborn Infant. Pediatrics 115: e508-e511 [Abstract] [Full Text]  
• Oberlander, T. F., Grunau, R. E., Fitzgerald, C., Papsdorf, M., Rurak, D., Riggs, W. (2005). Pain Reactivity in 2-Month-Old Infants After Prenatal and Postnatal Selective Serotonin Reuptake Inhibitor Medication Exposure. Pediatrics 115: 411-425 [Abstract] [Full Text]  
• SURI, R., ALTSHULER, L. A., MINTZ, J. (2004). Depression and the Decision to Abort. Am. J. Psychiatry 161: 1502-1502 [Full Text]  
• SUNDER, K., WISNER, K. L. (2004). Antidepressants and Premature Labor. Am. J. Psychiatry 161: 925-926 [Full Text]  
• Kallen, B. (2004). Neonate Characteristics After Maternal Use of Antidepressants in Late Pregnancy. Arch Pediatr Adolesc Med 158: 312-316 [Abstract] [Full Text]  
• Costa, L. G., Steardo, L., Cuomo, V. (2004). Structural Effects and Neurofunctional Sequelae of Developmental Exposure to Psychotherapeutic Drugs: Experimental and Clinical Aspects. Pharmacol. Rev. 56: 103-147 [Abstract] [Full Text]  
• Kim, J., Riggs, K. W., Rurak, D. W. (2004). STEREOSELECTIVE PHARMACOKINETICS OF FLUOXETINE AND NORFLUOXETINE ENANTIOMERS IN PREGNANT SHEEP. Drug Metab. Dispos. 32: 212-221 [Abstract] [Full Text]  
• Zeskind, P. S., Stephens, L. E. (2004). Maternal Selective Serotonin Reuptake Inhibitor Use During Pregnancy and Newborn Neurobehavior. Pediatrics 113: 368-375 [Abstract] [Full Text]  
• Laine, K., Heikkinen, T., Ekblad, U., Kero, P. (2003). Effects of Exposure to Selective Serotonin Reuptake Inhibitors During Pregnancy on Serotonergic Symptoms in Newborns and Cord Blood Monoamine and Prolactin Concentrations. Arch Gen Psychiatry 60: 720-726 [Abstract] [Full Text]  
• Pryse-Phillips, W., Yuen, D. E., Pham, B. (2003). Perinatal Outcome Following Third-Trimester Exposure to Paroxetine: An Alternative Interpretation. Arch Pediatr Adolesc Med 157: 601-601 [Full Text]  
• Simon, G. E., Cunningham, M. L., Davis, R. L. (2002). Outcomes of Prenatal Antidepressant Exposure. Am. J. Psychiatry 159: 2055-2061 [Abstract] [Full Text]  
• Begg, E. J., Duffull, S. B., Hackett, L. P., Ilett, K. F. (2002). Studying Drugs in Human Milk: Time to Unify the Approach. J Hum Lact 18: 323-332 [Abstract]  
• Nulman, I., Rovet, J., Stewart, D. E., Wolpin, J., Pace-Asciak, P., Shuhaiber, S., Koren, G. (2002). Child Development Following Exposure to Tricyclic Antidepressants or Fluoxetine Throughout Fetal Life: A Prospective, Controlled Study. Am. J. Psychiatry 159: 1889-1895 [Abstract] [Full Text]  
• Costei, A. M., Kozer, E., Ho, T., Ito, S., Koren, G. (2002). Perinatal Outcome Following Third Trimester Exposure to Paroxetine. Arch Pediatr Adolesc Med 156: 1129-1132 [Abstract] [Full Text]  
• Hendrick, V., Altshuler, L. (2002). Management of Major Depression During Pregnancy. Am. J. Psychiatry 159: 1667-1673 [Full Text]  
• Moore, T. R., Emanuel, A. M. (2001). Depression in Women across the Life Cycle. Journal of Pharmacy Practice 14: 511-525 [Abstract]  
• ISBISTER, G. K, DAWSON, A., WHYTE, I. M, PRIOR, F. H, CLANCY, C., SMITH, A. J, STISKAL, J. A, ITO, S. (2001). Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome?. Arch. Dis. Child. Fetal Neonatal Ed. 85: F145g-145 [Full Text]  
• Stiskal, J A, Kulin, N, Koren, G, Ho, T, Ito, S (2001). Neonatal paroxetine withdrawal syndrome. Arch. Dis. Child. Fetal Neonatal Ed. 84: 134F-135 [Abstract] [Full Text]  
• Committee on Drugs, (2000). Use of Psychoactive Medication During Pregnancy and Possible Effects on the Fetus and Newborn. Pediatrics 105: 880-887 [Abstract] [Full Text]  
• Moiseiwitsch, J. R.D. (2000). The Role of Serotonin and Neurotransmitters During Craniofacial Development. CROBM 11: 230-239 [Abstract] [Full Text]  
• Chambers, C. D., Anderson, P. O., Thomas, R. G., Dick, L. M., Felix, R. J., Johnson, K. A., Jones, K. L. (1999). Weight Gain in Infants Breastfed by Mothers Who Take Fluoxetine. Pediatrics 104: 61e-61 [Abstract] [Full Text]  
• Wisner, K. L., Gelenberg, A. J., Leonard, H., Zarin, D., Frank, E. (1999). Pharmacologic Treatment of Depression During Pregnancy. JAMA 282: 1264-1269 [Abstract] [Full Text]  
• Birnbaum, C. S., Cohen, L. S., Bailey, J. W., Grush, L. R., Robertson, L. M., Stowe, Z. N. (1999). Serum Concentrations of Antidepressants and Benzodiazepines in Nursing Infants: A Case Series. Pediatrics 104: 11e-11 [Abstract] [Full Text]  
• Spigset, O., Mårtensson, B. (1999). Fortnightly review: Drug treatment of depression. BMJ 318: 1188-1191 [Full Text]  
• Shearman, L. P., McReynolds, A. M., Zhou, F. C., Meyer, J. S. (1998). Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta. Am. J. Physiol. Cell Physiol. 275: C1621-C1629 [Abstract] [Full Text]  
• Cabrera-Vera, T. M., Battaglia, G. (1998). Prenatal Exposure to Fluoxetine (Prozac) Produces Site-Specific and Age-Dependent Alterations in Brain Serotonin Transporters in Rat Progeny: Evidence from Autoradiographic Studies. J. Pharmacol. Exp. Ther. 286: 1474-1481 [Abstract] [Full Text]  
• Goldstein, D. J., Yonkers, K. A., Halbreich, U., Brown, C., Pearlstein, T., Harrison, W., Endicott, J., Severino, S., Frank, E., Parry, B. (1998). Use of Serotonin Reuptake Inhibitors by Women of Childbearing Potential. JAMA 279: 1873-1874 [Full Text]  
• Bengel, D., Murphy, D. L., Andrews, A. M., Wichems, C. H., Feltner, D., Heils, A., Mössner, R., Westphal, H., Lesch, K.-P. (1998). Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine ("Ecstasy") in Serotonin Transporter-Deficient Mice. Mol. Pharmacol. 53: 649-655 [Abstract] [Full Text]  
• Kulin, N. A., Pastuszak, A., Sage, S. R., Schick-Boschetto, B., Spivey, G., Feldkamp, M., Ormond, K., Matsui, D., Stein-Schechman, A. K., Cook, L., Brochu, J., Rieder, M., Koren, G. (1998). Pregnancy Outcome Following Maternal Use of the New Selective Serotonin Reuptake Inhibitors: A Prospective Controlled Multicenter Study. JAMA 279: 609-610 [Abstract] [Full Text]  
• Cohen, L. S., Yonkers, K. A., Halbreich, U., Brown, C., Pearlstein, T., Freeman, E., Endicott, J., Severino, S., Frank, E. (1998). Sertraline for Premenstrual Dysphoric Disorder. JAMA 279: 357-358 [Full Text]  
• Mhanna, M. J., Bennet II, J. B., Izatt, S. D. (1997). Potential Fluoxetine Chloride (Prozac) Toxicity in a Newborn. Pediatrics 100: 158-158 [Full Text]  
• Cohen, L. S., Rosenbaum, J. F., Goldstein, D. J., Sundell, K. L., Corbin, L. A., Jones, K. L., Johnson, K. A., Chambers, C. D. (1997). Birth Outcomes in Pregnant Women Taking Fluoxetine. NEJM 336: 872-873 [Full Text]  
• Nulman, I., Rovet, J., Stewart, D. E., Wolpin, J., Gardner, H. A., Theis, J. G.W., Kulin, N., Koren, G. (1997). Neurodevelopment of Children Exposed in Utero to Antidepressant Drugs. NEJM 336: 258-262 [Abstract] [Full Text]  
• (1996). Birth Outcomes with Prenatal Fluoxetine. JWatch Psychiatry 1996: 10-10 [Full Text]  
• (1996). Prozac in Pregnancy. JWatch Women's Health 1996: 6-6 [Full Text]  
• (1996). BIRTH OUTCOMES WITH FLUOXETINE USE DURING PREGNANCY. JWatch General 1996: 3-3 [Full Text]  
• Robert, E. (1996). Treating Depression in Pregnancy. NEJM 335: 1056-1058 [Full Text]