Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
REVIEW

Fluoxetine during pregnancy: impact on fetal development

Janna L. Morrison A D , K. Wayne Riggs B and Dan W. Rurak C

A Discipline of Physiology, School of Molecular and Biomedical Science, Centre for the Early Origins of Adult Disease, University of Adelaide, Frome Rd, Adelaide, SA 5005, Australia.

B Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada.

C Department of Obstetrics and Gynecology, Faculty of Medicine, BC Research Institute for Children’s and Women’s Health, University of British Columbia, 950 West 28th Ave, Vancouver, BC, V5Z 4H4, Canada.

D Corresponding author. Email: janna.morrison@adelaide.edu.au

Reproduction, Fertility and Development 17(6) 641-650 https://doi.org/10.1071/RD05030
Submitted: 15 March 2005  Accepted: 12 June 2005   Published: 29 July 2005

Abstract

Women are at greatest risk of suffering from depression during the childbearing years and thus may either become pregnant while taking an antidepressant or may require a prescription for one during pregnancy. The antidepressant fluoxetine (FX) is a selective serotonin reuptake inhibitor (SSRI), which increases serotonin neurotransmission. Serotonin is involved in the regulation of a variety of physiological systems, including the sleep–wake cycle, circadian rhythms and the hypothalamic–pituitary–adrenal axis. Each of these systems also plays an important role in fetal development. Compared with other antidepressant drugs, the SSRIs, such as FX, have fewer side effects. Because of this, they are now frequently prescribed, especially during pregnancy. Clinical studies suggest poor neonatal outcome after exposure to FX in utero. Recent studies in the sheep fetus describe the physiological effects of in utero exposure to FX with an 8 day infusion during late gestation in the sheep. This is a useful model for determining the effects of FX on fetal physiology. The fetus can be studied for weeks in its normal intrauterine environment with serial sampling of blood, thus permitting detailed studies of drug disposition in both mother and fetus combined with monitoring of fetal behavioural state and cardiovascular function. Fluoxetine causes an acute increase in plasma serotonin levels, leading to a transient reduction in uterine blood flow. This, in turn, reduces the delivery of oxygen and nutrients to the fetus, thereby presenting a mechanism for reducing growth and/or eliciting preterm delivery. Moreover, because FX crosses the placenta, the fetus is exposed directly to FX, as well as to the effects of the drug on the mother. Fluoxetine increases high-voltage/non-rapid eye movement behavioural state in the fetus after both acute and chronic exposure and, thus, may interfere with normal fetal neurodevelopment. Fluoxetine also alters hypothalamic function in the adult and increases the magnitude of the prepartum rise in fetal cortisol concentrations in sheep. Fetal FX exposure does not alter fetal circadian rhythms in melatonin or prolactin. Studies of the effects of FX exposure on fetal development in the sheep are important in defining possible physiological mechanisms that explain human clinical studies of birth outcomes after FX exposure. To date, there have been insufficient longer-term follow-up studies in any precocial species of offspring exposed to SSRIs in utero. Thus, further investigation of the long-term consequences of in utero exposure to FX and other SSRIs, as well as the mechanisms involved, are required for a complete understanding of the impact of these agents on development. This should involve studies in both humans and appropriate animal models.


Acknowledgments

The authors thank the following for their participation in the original experiments discussed in the present review: Caly Chien, Nancy Gruber, Dave Kennaway and Caroline McMillen. JLM is funded by fellowships from the Heart and Stroke Foundation of Canada, the National Heart Foundation of Australia and the Maternal Fetal and Newborn Strategic Training Program at the University of Alberta.


References

Addis, A. , and Koren, G. (2000). Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol. Med. 30, 89–94.
CrossRef | PubMed |

Alvarez, J. C. , Gluck, N. , Arnulf, I. , Quintin, P. , Leboyer, M. , Pecquery, R. , Launay, J. M. , Perez-Diaz, F. , and Spreux-Varoquaux, O. (1999a). Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine. Clin. Pharmacol. Ther. 66, 617–624.
PubMed |

Alvarez, J. C. , Sanceaume, M. , Advenier, C. , and Spreux-Varoquaux, O. (1999b). Differential changes in brain and platelet 5-HT concentrations after steady-state achievement and repeated administration of antidepressant drugs in mice. Eur. Neuropsychopharmacol. 10, 31–36.
CrossRef | PubMed |

Andersson, L. , Sundstrom-Poromaa, I. , Wulff, M. , Astrom, M. , and Bixo, M. (2004a). Implications of antenatal depression and anxiety for obstetric outcome. Obstet. Gynecol. 104, 467–476.
PubMed |

Andersson, L. , Sundstrom-Poromaa, I. , Wulff, M. , Astrom, M. , and Bixo, M. (2004b). Neonatal outcome following maternal antenatal depression and anxiety: a population-based study. Am. J. Epidemiol. 159, 872–881.
CrossRef | PubMed |

Arnon, J. , Shechtman, S. , and Ornoy, A. (2000). The use of psychiatric drugs in pregnancy and lactation. Israel J. Psychiat. 37, 205–222.
PubMed |

Begg, E. J. , Duffull, S. B. , Saunders, D. A. , Buttimore, R. C. , Ilett, K. F. , Hackett, L. P. , Yapp, P. , and Wilson, D. A. (1999). Paroxetine in human milk. Br. J. Clin. Pharmacol. 48, 142–147.
CrossRef | PubMed |

Benfield, P. , Heel, R. C. , and Lewis, S. P. (1986). Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32, 481–508.
PubMed |

Boddy, K. , Dawes, G. S. , Fisher, R. , Pinter, S. , and Robinson, J. S. (1974). Foetal respiratory movements, electrocortical and cardiovascular responses to hypoxaemia and hypercapnia in sheep. J. Physiol. 243, 599–618.
PubMed |

Boland, R. , Joyce, B. J. , Wallace, M. J. , Stanton, H. , Fosang, A. J. , Pierce, R. A. , Harding, R. , and Hooper, S. B. (2004). Cortisol enhances structural maturation of the hypoplastic fetal lung in sheep. J. Physiol. 554, 505–517.
CrossRef | PubMed |

Byrd, R. A. , and Markham, J. K. (1994). Developmental toxicology studies of fluoxetine hydrochloride administered orally to rats and rabbits. Fund. Appl. Toxicol. 22, 511–518.
CrossRef | PubMed |

Calvo, G. , Garcia-Gea, C. , Luque, A. , Morte, A. , Dal-Re, R. , and Barbanoj, M. (2004). Lack of pharmacologic interaction between paroxetine and alprazolam at steady state in healthy volunteers. J. Clin. Psychopharmacol. 24, 268–276.
CrossRef | PubMed |

Casper, R. C. , Fleisher, B. E. , Lee-Ancajas, J. C. , Gilles, A. , Gaylor, E. , DeBattista, A. , and Hoyme, H. E. (2003). Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J. Pediatr. 142, 402–408.
CrossRef | PubMed |

Catterson, M. L. , and Preskorn, S. H. (1996). Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance. Pharmacol. Toxicol. 78, 203–208.
PubMed |

Chambers, C. D. , Johnson, K. A. , Dick, L. M. , Felix, R. J. , and Jones, K. L. (1996). Birth outcomes in pregnant women taking fluoxetine. N. Engl. J. Med. 335, 1010–1015.
CrossRef | PubMed |

Chambers, C. D. , Anderson, P. O. , Thomas, R. G. , Dick, L. M. , Felix, R. J. , Johnson, K. A. , and Jones, K. L. (1999). Weight gain in infants breastfed by mothers who take fluoxetine. Pediatrics 104, 61–66.
CrossRef | PubMed |

Chien, C. , Morrison, J. L. , Gruber, N. , Rurak, D. , and Riggs, K. W. (1999). Chronic exposure and pharmacokinetics of fluoxetine and norfluoxetine enantiomers in the pregnant ewe and fetus. AAPS PharmSci. 1, S224.


Clapp, J. F. , Szeto, H. H. , Abrams, R. , Larrow, R. , and Mann, L. I. (1980). Physiologic variability and fetal electrocortical activity. Am. J. Obstet. Gynecol. 136, 1045–1050.
PubMed |

Clark, K. E. , Mills, E. G. , Otte, T. E. , and Stys, S. J. (1980). Effect of serotonin on uterine blood flow in pregnant and nonpregnant sheep. Life Sci. 27, 2655–2661.
CrossRef | PubMed |

Cogill, S. R. , Caplan, H. L. , Alexandra, H. , Robson, K. M. , and Kumar, R. (1986). Impact of maternal postnatal depression on cognitive development of young children. Br. Med. J. (Clin. Res. Ed.) 292, 1165–1167.
PubMed |

Cohen, L. S. , and Rosenbaum, J. F. (1997). Birth outcomes in pregnant women taking fluoxetine. N. Engl. J. Med. 336, 872–873.
CrossRef | PubMed |

Cohen, L. S. , Heller, V. L. , Bailey, J. W. , Grush, L. , Ablon, J. S. , and Bouffard, S. M. (2000). Birth outcomes following prenatal exposure to fluoxetine. Biol. Psychiatry 48, 996–1000.
CrossRef | PubMed |

Condon, J. T. , and Corkindale, C. (1997). The correlates of antenatal attachment in pregnant women. Br. J. Med. Psychol. 70, 359–372.
PubMed |

Costei, A. M. , Kozer, E. , Ho, T. , Ito, S. , and Koren, G. (2002). Perinatal outcome following third trimester exposure to paroxetine. Arch. Pediatr. Adolesc. Med. 156, 1129–1132.
PubMed |

DeVane, C. L. (1999). Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors. Cell. Mol. Neurobiol. 19, 443–466.
CrossRef | PubMed |

DiPietro, J. A. , Costigan, K. A. , and Pressman, E. K. (2002). Fetal state concordance predicts infant state regulation. Early Hum. Dev. 68, 1–13.
CrossRef | PubMed |

Dole, N. , Savitz, D. A. , Hertz-Picciotto, I. , Siega-Riz, A. M. , McMahon, M. J. , and Buekens, P. (2003). Maternal stress and preterm birth. Am. J. Epidemiol. 157, 14–24.
CrossRef | PubMed |

Edwards, L. J. , and McMillen, I. C. (2002). Impact of maternal undernutrition during the periconceptional period, fetal number, and fetal sex on the development of the hypothalamo–pituitary–adrenal axis in sheep during late gestation. Biol. Reprod. 66, 1562–1569.
PubMed |

Emslie, G. , and Judge, R. (2000). Tricyclic antidepressants and selective serotonin reuptake inhibitors: use during pregnancy, in children/adolescents and in the elderly. Acta Psychiatr. Scand. Suppl. 403, 26–34.
PubMed |

Ener, R. A. , Meglathery, S. B. , Van Decker, W. A. , and Gallagher, R. M. (2003). Serotonin syndrome and other serotonergic disorders. Pain Med. 4, 63–74.
CrossRef | PubMed |

Epperson, N. , Jatlow, P. I. , Czarkowski, K. , and Anderson, G. M. (2003). Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother–infant pairs. Pediatrics 112, 425–429.
CrossRef |

Ericson, A. , Kallen, B. , and Wiholm, B. (1999). Delivery outcome after the use of antidepressants in early pregnancy. Eur. J. Clin. Pharmacol. 55, 503–508.
CrossRef | PubMed |

Fletcher, D. J. , Hanson, M. A. , Moore, P. J. , Nijhuis, J. G. , and Parkes, M. J. (1988). Stimulation of breathing movements by l-5-hydroxytryptophan in fetal sheep during normoxia and hypoxia. J. Physiol. 404, 575–589.
PubMed |

Giussani D. A., Fletcher A. J. W., Fowden A. L., and Gardner D. S. (2001). Ovine fetal cardiovascular, metabolic and endocrine response to hypoxaemia: difference between male and female fetuses. In ‘28th Annual Meeting of the Fetal and Neonatal Physiological Society, Auckland, New Zealand’. p. 102. (Fetal and Neonatal Physiological Society.)

Goldstein, D. J. (1995). Effects of third trimester fluoxetine exposure on the newborn. J. Clin. Psychopharmacol. 15, 417–420.
CrossRef | PubMed |

Goldstein, D. J. , Sundell, K. L. , and Corbin, L. A. (1997). Birth outcomes in pregnant women taking fluoxetine. N. Engl. J. Med. 336, 872–873.
PubMed |

Gupta, S. , Banfield, C. , Kantesaria, B. , Flannery, B. , and Herron, J. (2004). Pharmacokinetics/pharmacodynamics of desloratadine and fluoxetine in healthy volunteers. J. Clin. Pharmacol. 44, 1252–1259.
CrossRef | PubMed |

Heikkinen, T. , Ekblad, U. , Palo, P. , and Laine, K. (2003). Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation. Clin. Pharmacol. Ther. 73, 330–337.
CrossRef | PubMed |

Hendrick, V. , Smith, L. M. , Hwang, S. , Altshuler, L. L. , and Haynes, D. (2003a). Weight gain in breastfed infants of mothers taking antidepressant medications. J. Clin. Psychiatry 64, 410–412.
PubMed |

Hendrick, V. , Smith, L. M. , Suri, R. , Hwang, S. , Haynes, D. , and Altshuler, L. (2003b). Birth outcomes after prenatal exposure to antidepressant medication. Am. J. Obstet. Gynecol. 188, 812–815.
CrossRef | PubMed |

Hendrick, V. , Stowe, Z. N. , Altshuler, L. L. , Hwang, S. , Lee, E. , Haynes, D. , Heikkinen, T. , Ekblad, U. , Palo, P. , and Laine, K. (2003c). Placental passage of antidepressant medications: pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation. Am. J. Psychiatry 160, 993–996.
CrossRef | PubMed |

Hiemke, C. , and Hartter, S. (2000). Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol. Ther. 85, 11–28.
CrossRef | PubMed |

Hoffman, S. , and Hatch, M. C. (1996). Stress, social support and pregnancy outcome: a reassessment based on recent research. Paediatr. Perinat. Epidemiol. 10, 380–405.
PubMed |

Isbister, G. K. , Dawson, A. , Whyte, I. M. , Prior, F. H. , Clancy, C. , and Smith, A. J. (2001). Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch. Dis. Child. Fetal Neonatal Ed. 85, F147–F148.
PubMed |

Kallen, B. (2004). Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch. Pediatr. Adolesc. Med. 158, 312–316.
CrossRef | PubMed |

Kent, L. S. , and Laidlaw, J. D. (1995). Suspected congenital sertraline dependence. Br. J. Psychiatry 167, 412–413.
PubMed |

Kessler, R. C. , McGonagle, K. A. , Swartz, M. , Blazer, D. G. , and Nelson, C. B. (1993). Sex and depression in the National Comorbidity Survey. I: lifetime prevalence, chronicity and recurrence. J. Affect. Disord. 29, 85–96.
CrossRef | PubMed |

Kim, J. , Axelson, J. E. , Kearns, G. L. , Yin, W. , and Rurak, D. (1995). Stereoselcetive determination of fluoxetine and norfluxoetine with mass-selective detection (GC/MSD). Pharm. Res. 12, s22.


Kim, J. , Riggs, K. W. , and Rurak, D. W. (2004). Stereoselective pharmacokinetics of fluoxetine and norfluoxetine enantiomers in pregnant sheep. Drug Metab. Dispos. 32, 212–221.
CrossRef | PubMed |

Koren, G. (2002). SSRIs in pregnancy: are they safe? Pediatr. Res. 51, 424–425.
PubMed |

Koren, G. (2004). Discontinuation syndrome following late pregnancy exposure to antidepressants. Arch. Pediatr. Adolesc. Med. 158, 307–308.
CrossRef | PubMed |

Koren, G. , Nulman, I. , and Addis, A. (1998). Outcome of children exposed in utero to fluoxetine: a critical review. Depress. Anxiety 8(Suppl. 1), 27–31.
CrossRef | PubMed |

Kotzailias, N. , Marker, M. , and Jilma, B. (2004). Early effects of paroxetine on serotonin storage, plasma levels, and urinary excretion: a randomized, double-blind, placebo-controlled trial. J. Clin. Psychopharmacol. 24, 536–539.
CrossRef | PubMed |

Kristensen, J. H. , Ilett, K. F. , Dusci, L. J. , Hackett, L. P. , Yapp, P. , Wojnar-Horton, R. E. , Roberts, M. J. , and Paech, M. (1998). Distribution and excretion of sertraline and N-desmethylsertraline in human milk. Br. J. Clin. Pharmacol. 45, 453–457.
CrossRef | PubMed |

Kristensen, J. H. , Ilett, K. F. , Hackett, L. P. , Yapp, P. , Paech, M. , and Begg, E. J. (1999). Distribution and excretion of fluoxetine and norfluoxetine in human milk. Br. J. Clin. Pharmacol. 48, 521–527.
CrossRef | PubMed |

Laine, K. , Heikkinen, T. , Ekblad, U. , and 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.
CrossRef | PubMed |

Larsson, C. , Sydsjo, G. , and Josefsson, A. (2004). Health, sociodemographic data, and pregnancy outcome in women with antepartum depressive symptoms. Obstet. Gynecol. 104, 459–466.
PubMed |

Lawrenson, R. A. , Tyrer, F. , Newson, R. B. , and Farmer, R. D. (2000). The treatment of depression in UK general practice: selective serotonin reuptake inhibitors and tricyclic antidepressants compared. J. Affect. Disord. 59, 149–157.
CrossRef | PubMed |

Ledward, R. S. (1996). Drugs in pregnancy. Prog. Obstet. Gynecol. 12, 19–46.


Marcus, S. M. , Flynn, H. A. , Blow, F. C. , and Barry, K. L. (2003). Depressive symptoms among pregnant women screened in obstetrics settings. J. Womens Health 12, 373–380.
PubMed |

Martin, J. A. , Hamilton, B. E. , Ventura, S. J. , Menacker, F. , Park, M. M. , and Sutton, P. D. (2002). Births: final data for 2001. Natl Vital Stat. Rep. 51, 1–102.
PubMed |

McCormick, M. C. , Brooks-Gunn, J. , Shorter, T. , Holmes, J. H. , Wallace, C. Y. , and Heagarty, M. C. (1990). Factors associated with smoking in low-income pregnant women: relationship to birth weight, stressful life events, social support, health behaviors and mental distress. J. Clin. Epidemiol. 43, 441–448.
CrossRef | PubMed |

McElhatton, P. R. , Garbis, H. M. , Elefant, E. , Vial, T. , and Bellemin, B. , et al. (1996). The outcome of pregnancy in 689 women exposed to therapeutic doses of antidepressants. A collaborative study of the European Network of Teratology Information Services (ENTIS). Reprod. Toxicol. 10, 285–294.
CrossRef | PubMed |

McIntosh, G. H. , Baghurst, K. I. , Potter, B. J. , and Hetzel, B. S. (1979). Foetal brain development in the sheep. Neuropathol. Appl. Neurobiol. 5, 103–114.
PubMed |

Morin, L. P. (1999). Serotonin and the regulation of mammalian circadian rhythmicity. Ann. Med. 31, 12–33.
PubMed |

Morrison, J. L. , Carmichael, L. , Homan, J. , and Richardson, B. S. (1997). The effects of ‘sleep promoting agents’ on behavioural state in the ovine fetus. Brain Res. Dev. Brain Res. 103, 1–8.
CrossRef | PubMed |

Morrison, J. L. , Chien, C. , Gruber, N. , Rurak, D. , and Riggs, W. (2001). Fetal behavioural state changes following maternal fluoxetine infusion in sheep. Dev. Brain Res. 131, 47–56.
CrossRef |

Morrison, J. L. , Chien, C. , Riggs, K. W. , Gruber, N. , and Rurak, D. (2002). Effect of maternal fluoxetine administration on uterine blood flow, fetal blood gas status, and growth. Pediatr. Res. 51, 433–442.
PubMed |

Morrison, J. L. , Riggs, K. W. , Chien, C. , Gruber, N. , McMillen, I. C. , and Rurak, D. W. (2004). Chronic maternal fluoxetine infusion in pregnant sheep: effects on the maternal and fetal hypothalamic–pituitary–adrenal axes. Pediatr. Res. 56, 40–46.
CrossRef | PubMed |

Morrison, J. L. , Rurak, D. , Chien, C. , Kennaway, D. J. , Gruber, N. , McMillen, I. C. , and Riggs, K. W. (2005). Maternal fluoxetine infusion does not alter fetal endocrine and biophysical circadian rhythms in pregnant sheep. J. Soc. Gynecol. Investig. 12, 356–364.
CrossRef | PubMed |

Mourilhe, P. , and Stokes, P. E. (1998). Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. Drug Saf. 18, 57–82.
PubMed |

Newnham, J. P. , Moss, T. J. , Nitsos, I. , and Sloboda, D. M. (2002). Antenatal corticosteroids: the good, the bad and the unknown. Curr. Opin. Obstet. Gynecol. 14, 607–612.
CrossRef | PubMed |

Noble, R. E. (2005). Depression in women. Metabolism 54, 49–52.
CrossRef | PubMed |

Nordeng, H. , Lindemann, R. , Perminov, K. V. , and Reikvam, A. (2001). Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 90, 288–291.
CrossRef | PubMed |

Nulman, I. , Rovet, J. , Stewart, D. E. , Wolpin, J. , Gardner, H. A. , Theis, J. G. , Kulin, N. , and Koren, G. (1997). Neurodevelopment of children exposed in utero to antidepressant drugs. N. Engl. J. Med. 336, 258–262.
CrossRef | PubMed |

Nulman, I. , Rovet, J. , Stewart, D. E. , Wolpin, J. , Pace-Asciak, P. , Shuhaiber, S. , and 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.
CrossRef | PubMed |

Oberlander, T. F. , Grunau, R. E. , Fitzgerald, C. , Ellwood, E. L. , Misri, S. , Rurak, D. , and Riggs, K. W. (2002). Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr. Res. 51, 443–453.
PubMed |

Oberlander, T. F. , Grunau, R. E. , Fitzgerald, C. , Papsdorf, M. , Rurak, D. , and Riggs, W. (2005). Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 115, 411–425.
CrossRef | PubMed |

O’Hara, M. W. , Neunaber, D. J. , and Zekoski, E. M. (1984). Prospective study of postpartum depression: prevalence, course, and predictive factors. J. Abnorm. Psychol. 93, 158–171.
CrossRef | PubMed |

Orr, S. T. , and Miller, C. A. (1995). Maternal depressive symptoms and the risk of poor pregnancy outcome. Review of the literature and preliminary findings. Epidemiol. Rev. 17, 165–171.
PubMed |

Orr, S. T. , James, S. A. , and Blackmore Prince, C. (2002). Maternal prenatal depressive symptoms and spontaneous preterm births among African–American women in Baltimore, Maryland. Am. J. Epidemiol. 156, 797–802.
CrossRef | PubMed |

Ortiz, J. , and Artigas, F. (1992). Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine. Br. J. Pharmacol. 105, 941–946.
PubMed |

Palmer, S. K. , Zamudio, S. , Coffin, C. , Parker, S. , Stamm, E. , and Moore, L. G. (1992). Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet. Gynecol. 80, 1000–1006.
PubMed |

Pastuszak, A. , Schick-Boschetto, B. , Zuber, C. , Feldkamp, M. , and Pinelli, M. , et al. (1993). Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). JAMA 269, 2246–2248.
CrossRef | PubMed |

Peacock, J. L. , Bland, J. M. , and Anderson, H. R. (1995). Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine. BMJ 311, 531–535.
PubMed |

Philipps, L. H. , and O’Hara, M. W. (1991). Prospective study of postpartum depression: 4½-year follow-up of women and children. J. Abnorm. Psychol. 100, 151–155.
CrossRef | PubMed |

Pillai, M. , and James, D. (1990). Development of human fetal behavior: a review. Fetal Diagn. Ther. 5, 15–32.
PubMed |

Prosser, R. A. (2000). Serotonergic actions and interactions on the SCN circadian pacemaker: in vitro investigations. Biol. Rhythm Res. 31, 315–339.
CrossRef |

Quilligan, E. J. , Clewlow, F. , Johnston, B. M. , and Walker, D. W. (1981). Effect of 5-hydroxytryptophan on electrocortical activity and breathing movements of fetal sheep. Am. J. Obstet. Gynecol. 141, 271–275.
PubMed |

Rampono, J. , Kristensen, J. H. , Hackett, L. P. , Paech, M. , Kohan, R. , and Ilett, K. F. (2000). Citalopram and demethylcitalopram in human milk: distribution, excretion and effects in breast fed infants. Br. J. Clin. Pharmacol. 50, 263–268.
CrossRef | PubMed |

Rampono, J. , Proud, S. , Hackett, L. P. , Kristensen, J. H. , and Ilett, K. F. (2004). A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate. Int. J. Neuropsychopharmacol. 7, 329–334.
CrossRef | PubMed |

Rementeria, J. L. , and Bhatt, K. (1977). Withdrawal symptoms in neonates from intrauterine exposure to diazepam. J. Pediatr. 90, 123–126.
PubMed |

Richardson B. S. (1994). Ontogeny of behavioural states in the fetus. In ‘Textbook of Fetal Physiology’. (Eds G. D. Thornburn and R. Harding.) pp. 322–328. (Oxford University Press: Oxford, UK.)

Robert, E. (1996). Treating depression in pregnancy. N. Engl. J. Med. 335, 1056–1058.
CrossRef | PubMed |

Roberts, C. L. , and Lancaster, P. A. (1999). Australian national birthweight percentiles by gestational age. Med. J. Aust. 170, 114–118.
PubMed |

Roffwarg, H. P. , Muzio, J. N. , and Dement, W. C. (1966). Ontogenetic development of the human sleep–dream cycle. Science 152, 604–619.


Rossi, A. , Barraco, A. , and Donda, P. (2004). Fluoxetine: a review on evidence based medicine. Ann. Gen. Hosp. Psychiatry 3, 2–9.
CrossRef | PubMed |

Sanz, E. J. , De-las-Cuevas, C. , Kiuru, A. , Bate, A. , and Edwards, R. (2005). Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 365, 482–487.
PubMed |

Scharf, A. , Seppelt, M. , and Sohn, C. (2003). Doppler flow velocity to measure the redistribution of fetal cardiac output in fetal stress. Eur. J. Obstet. Gynecol. Reprod. Biol. 110, S119–S126.
CrossRef | PubMed |

Schwartz, J. , and McMillen, I. C. (2001). Fetal hypothalamus–pituitary–adrenal axis on the road to parturition. Clin. Exp. Pharmacol. Physiol. 28, 108–112.
CrossRef | PubMed |

Shader, R. I. (1992a). Does continuous use of fluoxetine during the first trimester of pregnancy present a high risk for malformation or abnormal development to the exposed fetus? J. Clin. Psychopharmacol. 12, 441.
PubMed |

Shader, R. I. (1992b). A patient of mine missed a period while taking fluoxetine; it turned out that she was not pregnant. However, the question arose about the safety of fluoxetine during pregnancy. What is known? J. Clin. Psychopharmacol. 12, 213.
PubMed |

Silvestri, R. , Pace-Schott, E. F. , Gersh, T. , Stickgold, R. , Salzman, C. , and Hobson, J. A. (2001). Effects of fluvoxamine and paroxetine on sleep structure in normal subjects: a home-based nightcap evaluation during drug administration and withdrawal. J. Clin. Psychiatry 62, 642–652.
PubMed |

Simon, G. E. , Cunningham, M. L. , and Davis, R. L. (2002). Outcomes of prenatal antidepressant exposure. Am. J. Psychiatry 159, 2055–2061.
CrossRef | PubMed |

Speight, A. N. (1977). Floppy-infant syndrome and maternal diazepam and/or nitrazepam. Lancet 310, 878.
CrossRef | PubMed |

Spencer, M. J. (1993). Fluoxetine hydrochloride (Prozac) toxicity in a neonate. Pediatrics 92, 721–722.
PubMed |

Stanford, M. S. , and Patton, J. H. (1993). In utero exposure to fluoxetine HCl increases hematoma frequency at birth. Pharmacol. Biochem. Behav. 45, 959–962.
CrossRef | PubMed |

Steer, R. A. , Scholl, T. O. , Hediger, M. L. , and Fischer, R. L. (1992). Self-reported depression and negative pregnancy outcomes. J. Clin. Epidemiol. 45, 1093–1099.
CrossRef | PubMed |

Stiskal, J. A. , Kulin, N. , Koren, G. , Ho, T. , and Ito, S. (2001). Neonatal paroxetine withdrawal syndrome. Arch. Dis. Child. Fetal Neonatal Ed. 84, F134–F135.
CrossRef | PubMed |

Stokes, P. E. , and Holtz, A. (1997). Fluoxetine tenth anniversary update: the progress continues. Clin. Ther. 19, 1135–1250.
CrossRef | PubMed |

Suri, R. , Altshuler, L. , Hendrick, V. , Rasgon, N. , Lee, E. , and Mintz, J. (2004). The impact of depression and fluoxetine treatment on obstetrical outcome. Arch. Women Ment. Health 7, 193–200.
PubMed |

Tabor, B. L. , Lewis, J. F. , Ikegami, M. , Polk, D. , and Jobe, A. H. (1994). Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs. Pediatr. Res. 35, 479–483.
PubMed |

Thase, M. E. (1998). Depression, sleep, and antidepressants. J. Clin. Psychiatry 59, 55–65.
PubMed |

Ursin, R. (2002). Serotonin and sleep. Sleep Med. Rev. 6, 55–69.
CrossRef | PubMed |

Vorhees, C. V. , Acuff-Smith, K. D. , Schilling, M. A. , Fisher, J. E. , Moran, M. S. , and Buelke-Sam, J. (1994). A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Fundam. Appl. Toxicol. 23, 194–205.
CrossRef | PubMed |

Weissman, M. M. , and Olfson, M. (1995). Depression in women: implications for health care research. Science 269, 799–801.
PubMed |

Wen, S. W. , and Walker, M. (2004). The use of selective serotonin reuptake inhibitors in pregnancy. J. Obstet. Gynaecol. Can. 26, 819–822.
PubMed |

Wood C. E. (1994). The function of the fetal pituitary–adrenal system. In ‘Textbook of Fetal Physiology’. (Eds G. D. Thornburn and R. Harding.) pp. 351–358. (Oxford University Press: Oxford, UK.)

Yoshioka, T. , Inomata, K. , Sugioka, K. , and Nakamura, K. (1980). Ultrastructural study on myelination in rat spinal cord during the early postnatal stage. Brain Dev. 2, 337–343.
PubMed |

Zemdegs, I. Z. , McMillen, I. C. , Walker, D. W. , Thorburn, G. D. , and Nowak, R. (1988). Diurnal rhythms in plasma melatonin concentrations in the fetal sheep and pregnant ewe during late gestation. Endocrinology 123, 284–289.
PubMed |

Zeskind, P. S. , and Stephens, L. E. (2004). Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 113, 368–375.
CrossRef | PubMed |



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