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Traditionally, pregnancy has been thought of as a period of well-being and happiness. The pregnancy state itself has been thought to protect women from depression (1,2). However, women of child-bearing age frequently suffer from major depression (3,4). Lifetime depression risk estimates in community-derived samples have varied between 10% and 25% of pregnant women (5–7). Two recent studies that screened obstetric patients at random for depressive symptoms found that 20% of patients actually met criteria for a diagnosis of depression (8,9). Antepartum depression is also common in women with a history of depressive illness, such that some researchers now believe pregnancy to be a risk factor for a mood disorder in those with such a history (10–12). Despite the prevalence of depression during pregnancy and the growing body of literature associated with its treatment, whether pharmacologic or otherwise, large numbers of women are untreated. A 2003 study by Marcus and others found that 1 in 5 pregnant women experience depression but that few seek treatment (12). This large study of 3472 pregnant obstetric clinic patients revealed both underdiagnosis and undertreatment of depression during pregnancy: 20% of obstetric patients scored high on the Centre for Epidemiologic Studies Depression Scale (CESD). Although CESD scores do not by themselves diagnose clinical depression, only 13.8% of these women were receiving any form of mental health care. The remaining 86.2% of women with depressive symptoms were not receiving any treatment at all (defined as medication, psychotherapy, or counselling). Over one-half of the women in the study had been taking medications for depression and had stopped once they conceived. These results are similar to another 2003 study, which found a 20% depression rate in random screening for depression among pregnant women in a hospital obstetric setting (9). In that study, fewer than 21% of the women with depression were receiving treatment. The Marcus and others study concluded that the stigma of having depression during pregnancy may prevent women from seeking active treatment—women may feel guilty for suffering during what is supposed to be a happy period (12). In this review, our objective was to summarize the state of knowledge about depression during pregnancy. We focused on some of the major consequences of untreated maternal depression. MethodsWe searched Medline and medical texts for studies pertaining to depression during pregnancy published up to the end of April 2003. We included the MeSH phrases depression and pregnancy, depression and pregnancy outcome, and depression and untreated and pregnancy. We reviewed only English-language papers. We restricted the review to original human and animal studies and did not consider case reports or letters to the editor. We excluded studies dealing with bipolar depression.
Etiology of Poor Pregnancy Outcome in Depression PatientsDepression has been recognized as a disease that affects fetal health (13). Although both psychological and biological explanations have been proposed, hormonal hypotheses have received the most attention. Depression has been associated with hypothalamo–pituitary–adrenal (HPA) axis hyperactivity. Maternal stress, anxiety, or depression, which are regulated by peptides derived from the activated HPA axis (14–19), are all thought to influence birth outcome. This increased HPA-axis activity may directly affect fetal growth. Maternal depression may not only activate the mother’s HPA axis; it may in turn cause an increase in the release of corticotropin-releasing hormone (CRH) from the placenta via the actions of catecholamines and cortisol. CRH may also influence the timing and onset of delivery, which could explain why women suffering from depression show higher rates of premature labour (16,17). Animal studies have found that stress during pregnancy is associated with dysfunction of the HPA axis and subsequent abnormal development of fetal tissue (10,18,20). An alternate hypothesis asserts that depression alters excretion of vasoactive hormones and neuro- endocrine transmitters, which then induce vascular changes in a pregnant woman (21). To support the HPA-axis hypothesis of depression’s impact on pregnancy, the relation between mood changes and obstetric experience and alterations in plasma cortisol, beta- endorphin, and CRH were examined in 97 women (18). Plasma levels of these hormones were obtained throughout pregnancy, at delivery, and postpartum. Mood disturbance rates were highest at 38 weeks’ gestation, while plasma hormone levels rose throughout the pregnancy and peaked before labour. Cortisol, beta-endorphin, and CRH climbed significantly throughout the pregnancy and were highly correlated to one another. Those women with the highest clinical depression scores were given significantly more pain relief during labour. This may also be related to endorphin levels, which rise throughout pregnancy and fall dramatically during delivery. In line with previous studies, higher rates of mood disturbance were found in the late antenatal period than in the postnatal period; this correlated with hormone levels, which peaked in late pregnancy and fell postpartum (18). These data suggest a role for CRH and the HPA axis in the interaction between antenatal mood states and obstetric events. Although the existing literature suggests various ways in which hormonal deviations may affect pregnant women, much remains unclear in regard to defining the mechanisms by which depression adversely affects pregnancy outcome. Risks of Untreated Depression During PregnancyWhile conflicting studies exist that either stress or dispute the significance of obstetric complications in women with depression (22,23), it is well recognized that there is maternal morbidity and mortality associated with untreated mental conditions (24–28), including suicide attempts (37). Most researchers have found that untreated depression may have associated obstetric complications and puerperal pathologies (3,13,17,21,29–36). It has been suggested that mental illness may affect a pregnancy by affecting the mother’s emotional state. The prevalent idea is that psychopathological symptoms during pregnancy have physiological consequences for the fetus. Gestational hypertension and subsequent preeclampsia have also been linked to mothers with untreated depression during pregnancy (15,21). Untreated depression during pregnancy has been associated with such adverse outcomes as spontaneous abortion (37), bleeding during gestation (38), increased uterine artery resistance (39), low Apgar scores (36), admission to a neonatal care unit (13), neonatal growth retardation (13,40,41), spontaneous early labour (42,43), fetal death (36), low birth weight in babies (15,17,34,38,44), babies small for their gestational age (34,38,41), perinatal and birth complications (15,38,45), preterm deliveries (13,17,35,42,43,46), and high cortisol levels in offspring at birth (40,47). Depression has also been linked to such operative deliveries as cesarean section or vaginal instrumental (13) and to a subjective description of labour as more painful and therefore more commonly needing epidural analgesia (18,48). Physiology aside, studies have found that mental illness can affect a mother’s functional status, her ability to obtain prenatal care, and her ability to avoid unhealthy behaviour. Women suffering from depression are more likely to smoke or use alcohol or other substances, which may confound pregnancy outcome (49). In this review, we discuss all the above outcomes more thoroughly. One of the most obvious concerns regarding untreated depression during pregnancy is worsening of the condition itself, which may lead to suicide ideation or attempts. Untreated antenatal depression may be associated with a 50% to 62% risk of a postpartum episode and a worsening of the psychiatric condition (50,51). Termination of pregnancy on psychiatric grounds is common (52,53). According to the National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression, 15% of women who do not treat their depression during pregnancy attempt suicide (54,55), while 50% to 62% continue to suffer from depression in the postpartum period (55). Suicide attempts during pregnancy have been described (54,56). It has been estimated that depression may be responsible for 30 000 to 35 000 suicides yearly in North America (55). Preterm Delivery and Growth RetardationIt has been proposed that psychopathology during pregnancy adversely affects the uterine environment and therefore affects fetal outcome (51). Steer and others found elevated risks for preterm delivery (< 37 weeks), low birth weight (< 2500 g), and babies small for their gestational age (< 10th percentile) among women who had scores of 21 or more on the Beck Depression Inventory (BDI) and who were not receiving active treatment (34). These researchers also regressed the BDI scores of 389 pregnant women to indicators of poor pregnancy outcome. Among these women, the risk of a poor outcome rose 5% to 7% (P < 0.05) for each point by which the BDI total score increased (34). In other studies, prenatal stress and depression have been similarly significantly associated with lower infant birth weight and gestational age at birth (34,35,44,57,58). A recent study of women with lower socioeconomic status found depression to be associated with restricted fetal growth and babies small for their gestational age (41). A clear association has been found between increased hypothalamic, pituitary, and placental hormones and the occurrence of preterm labour (42,46). Recent studies have suggested that maternal depression is linked with smaller head circumference and lower Apgar scores in offspring (10,32,36). Of growing concern is the effect of perinatal depression on fetoplacental integrity and fetal CNS development (59). PreeclampsiaStudies have also investigated the link between depression and preeclampsia. Defined as blood pressure higher than 140/100 mm Hg and proteinuria, preeclampsia is a serious pregnancy complication. Strenuous work, depression, and anxiety may increase the risk for this condition, whereas the stress of daily living has not been associated with it. Kurki and colleagues studied 623 nulliparous Finnish women at low risk for preeclampsia. All women had a healthy first trimester and were then tested with standard Beck Depression and Anxiety scales at a median 12 weeks (21). Depression was detected in 30% of the women, which matches with the known prevalence of depression during pregnancy in the Finnish population (21). Anxiety was detected in 16%, and proteinuric preeclampsia was detected in 4.5%. Depression was associated with an increased risk for preeclampsia (odds ratio 2.5; 95%CI, 1.2 to 5.3), as was anxiety. However, this risk did not increase with higher BDI scores. Multiple logistic regression found depression to be associated with 2.5-fold increased risk for preeclampsia and either depression or anxiety to be associated with a 3.1-fold increased risk for this condition. Depression and anxiety may be harmful through an altered excretion of vasoactive hormones and other neuroendocrine transmitters. This may in turn cause vasoconstriction and uterine artery resistance and, therefore, elevate blood pressure (17,21). Spontaneous AbortionSeveral studies have suggested that depression may be a risk factor for spontaneous abortion (29,37,60,61). Stress and hormones associated with depression, such as CRH and adrenocorticotrophic hormone (ACTH), may interact with T cells or mast cells to produce changes in cytokine production. Because a balance in the nervous and endocrine systems is required to maintain pregnancy, the imbalance caused by depression may be abortogenic (29,61,62). Miscarriage has been hypothesized to be caused by a Th1–Th2 cytokine imbalance, which is suspected to be influenced by psychological factors. Cytokines may play protective roles during pregnancy, and a shift in their relative amounts is thought to activate coagulation, lead to vasculitis, and affect maternal blood supply to the embryo, thereby producing ischemic autoamputation and miscarriage. Psychological influences on the endocrine and immune systems have been examined, suggesting that a pregnant woman’s psychological state can mediate pregnancy outcome through these body systems (15). While women who experience recurrent spontaneous abortions may present with psychological disorders, whether depression is a causal factor in abortion or whether it is a result is under debate. Several published studies have shown that emotional distress may be associated with recurrent spontaneous abortions and reproductive failure (37,62). Conversely, other studies failed to show such association (60). In a recent study, “women’s neuroticism” and current depressive symptoms were found to be negatively correlated with natural killer-cell activity, which is thought to predict miscarriage. Studies have even suggested that pre- and periconceptional psychological state may affect the number of oocytes retrieved and fertilized, as well as a woman’s pregnancy and delivery outcome (13). A study by Sugiura-Ogasawara and others examined whether psychosocial factors influence subsequent miscarriages in women experiencing spontaneous recurrent abortions. Women with a history of 2 or more miscarriages and no live births received a mental status assessment according to the Symptom Checklist-90-Revised (SCL-90-R) psychopathology scale. Data were then examined to see whether women’s personality traits (including depression) could predict subsequent miscarriage. Twenty-two percent of participants miscarried, and the miscarriage rate was positively associated with current depression (P = 0.004), neuroticism, interpersonal sensitivity, and psychosis. Only depression showed a statistically significant predictive value for miscarriage. Since it is widely accepted that acute and chronic stress can affect the immune system, this study suggests that the chronic stress of depression may be associated with altered immune system factors, which may affect pregnancy viability (62). Fetal PhysiologyUltrasonography has been used to suggest that the fetus of a mother suffering from depression spends more time in sleep and exhibits less body movement than the fetus of a mother without depression (13). A similar study using ultrasonography suggested that maternal depression may affect fetal heart rate response to vibroacoustic stimulation (59). This test produces cardio acceleration typical of a healthy fetus and is commonly used to assess fetal well-being. In women with untreated depression, there was a delayed fetal response to a vibroacoustic stimulus applied to the maternal abdomen. In women with depressed BDI scores, fetal heart rate response was reduced. According to the investigators, this could signal alterations in the internal hormonal environment that have implications for postnatal information processing (59). Maternal Health-Related BehaviourIt has also been postulated that depression may lead to unhealthy behaviours that can indirectly affect obstetric outcome: depression can manifest in unhealthy lifestyle and coping behaviours during pregnancy; these may then mediate birth outcome (15,49). Mental illness may also cause cognitive distortions that affect decision-making capacities; it may therefore be associated with poor attendance at antenatal clinics and substance abuse (49,63). Zuckerman and colleagues found a significant association between depressive symptoms during pregnancy and the use of cigarettes, alcohol, and cocaine (49). Pregnant women with depression are more likely to lack volition to follow physician care regimes. They may not be as well nourished, show affected capacity to make decisions, and suffer from reduced sleep; they may also engage in more unhealthy behaviours than women who do not suffer from depression. Women with depression may suffer from problems in social function, emotional withdrawal, and excessive concern regarding their future ability to parent (15). They may report excessive worry about pregnancy and are less likely to regularly attend obstetrical visits or have regular ultrasounds. Because they tend to present with diminished appetite, they therefore have lower-than-normal weight gain throughout pregnancy. They may also demonstrate poor self-care and lack of compliance with prenatal care. Conversely, women without depression are more likely to be proactive about health care in pregnancy (15). Women with depression tend to use prenatal vitamins less often than women without depression and to be less informed about the value of folic acid (49). Women suffering from depression show lack of initiative and motivation to seek help, as well as a negative perception regarding any potential benefit of obstetric services (49,64). These behaviours may all increase the risk for adverse pregnancy outcome. Severe depression also carries the risk of self-injurious, psychotic, impulsive, and harmful behaviours. If left untreated, depression during pregnancy has been known to deteriorate into acute forms of other psychiatric disturbances (4). Perinatal DevelopmentStress during pregnancy has a suggested association with delayed developmental milestones in offspring (as well as with clinging, crying, hyperactivity, low frustration threshold, unsocial behaviour, schizophrenia, and attention-deficit hyperactivity disorder) (46). Depression during pregnancy is currently being studied in this context (65). Neonatal Neurobehavioural EffectsFollowing birth, depression in women may be associated with reduced attachment, reduced parent–child bonding, and delays in offsprings’ cognitive and emotional development (10,66–68). Lower language achievements and long-term behavioural problems may also be seen in some children whose mothers suffered from depression (66). Mothers suffering from depression report inability to carry out maternal duties far more often than do their counterparts without depression, and their infants show irritability, hostility, and erratic sleep (40), as well as an enhanced stress response (66). Infants whose mothers suffer from depression have been found to have reduced brain electrical activity across the left frontal lobe, a region of the brain associated with such positive emotions as joy. A review by Wisner and others argued that untreated depression is associated with inconsolability and excessive crying of offspring at birth (65). Maternal state of mind may powerfully affect parenting behaviour, even immediately following birth. It has also been speculated that, owing to disruptions in the caretaking environment, children of mothers with depression are at increased risk for internalizing problems (65). Such children reported more internalizing symptoms on the Dominic Interactive questionnaire, a pediatric DSM-III-R mental disorders scale (47). In a study by Nulman and colleagues, postpartum maternal depression—not the use of fluoxetine or tricyclic antidepressants during pregnancy—predicted lower cognitive and language development in preschool offspring (69). Infant Stress Hormone LevelsOne study investigated the stress hormone levels of children whose mothers suffered from depression (47). The hypothesis underlying this study was that disruptions in early caretaking could have long-term repercussions for the HPA axis, which mediates stress response. Salivary cortisol levels were measured in offspring of mothers with and without depression. These samples were taken after arrival at the laboratory, after a laboratory stressor, and during a normal day outside the laboratory. Offspring of mothers with depression showed elevated baseline cortisol levels as well as elevated response to the stressor. In response to a fear-potentiated paradigm, children of mothers with depression had a higher cortisol elevation. This study concluded that maternal depression in the first 2 years of life may be associated with high cortisol levels in offspring. That elevated cortisol is found in children of mothers suffering from depression has also been noted in another study (40). These findings suggest increased baseline stress and decreased coping with stressors that present in the child’s life. Psychopathology in OffspringIn other studies, children of mothers suffering from depression showed an increased risk of behavioural and emotional problems, including affective disorders. A 2003 study has also suggested a significant association with criminality in offspring of mothers with antenatal untreated depression (70). Further, studies have found that these children are 6 times more likely to develop depression than are children of mothers without depression, suggesting that genetic susceptibility has a role, in addition to environment (71). ConclusionThe biological dysregulation that occurs in depression may not be ideal for pregnancy. Despite this, most studies tend to focus on the risks to obstetric outcome of psychotropic medications, rather than on the risks of untreated depression. Very few studies consider nonpharmacologic therapy during pregnancy. This imbalance may lead women who suffer from depression to refuse treatment because they fear teratogenic effects. They are not aware that they potentially put their pregnancy and their baby at risk, especially when so few receive psychotherapy. When patients refuse treatment during pregnancy, we recommend that they be monitored to assess for such possible adverse outcomes as suicidal tendencies, deteriorating social functions, psychosis, and inability to comply with obstetrical evaluations (5). Given the potential impact of antenatal mental disturbances on maternal and infant outcomes, pregnant women require further psychiatric evaluation and treatment within the obstetrical sector. The perinatal period can become a critical time to screen for and identify depression, since pregnant women have increased contact with health services. Finally, when making clinical decisions, clinicians should weigh the growing body of literature suggesting potential adverse effects of untreated depression during pregnancy against the literature that has failed to find risks associated with in utero antidepressant exposure. Funding and SupportLori Bonari was supported by a grant from the Ontario Graduate Scholarship and the Hospital for Sick Children Research Training Competition. The study was supported by a grant from the Council of Ontario Women’s Health. References1. [Anonymous]. Pregnancy depression. Lancet 1984;2(8396):206. 2. Buist A. Managing depression in pregnancy. Aust Fam Physician 2000;29:663–7. 3. D’Alfonso A, Iovenitti P, Casacchia M, Carta G. Disturbances of humour in postpartum: our experience. Clin Exp Obstet Gynecol 2002;29:207–11. 4. Stocky A, Lynch J. Acute psychiatric disturbance in pregnancy and the puerperium. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14(1):73–87. 5. Wisner KL, Zarin DA, Holmboe ES, Appelbaum PS, Gelenberg AJ, Leonard HL, and others. Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 2000;157:1933–40. 6. Llewellyn AM, Stowe ZN, Nemeroff CB. Depression during pregnancy and the puerperium. J Clin Psychiatry 1997;58 (Suppl 15):26–32. 7. Kessler, McGonagle KA, Swartz M. Sex and depression in the National Comorbidity Survey I: lifetime prevalence, chronicity and recurrence. J Affect Disord 1993;29:85–96. 8. Birndorf CA, Madden A, Portera L, Leon AC. Psychiatric symptoms, functional impairment, and receptivity toward mental health treatment among obstetrical patients. Int J Psychiatry Med 2001;355–65. 9. Scholle SH, Haskett RF, Hanusa BH, Pincus HA, Kupfer DJ. Addressing depression in obstetrics/gynecology practice. Gen Hosp Psychiatry 2003;25(2):83–90. 10. Nonacs R, Cohen LS. Depression during pregnancy: diagnosis and treatment options. J Clin Psychiatry 2002;63(7):24–30. 11. Altshuler LL, Hendrick V, Cohen LS. Course of mood and anxiety disorders during pregnancy and the postpartum period. J Clin Psychiatry 1998;59 (Suppl 2):29–33. 12. Marcus SM, Flynn HA, Blow FC, Barry KL. Depressive symptoms among pregnant women screened in obstetrics settings. J Womens Health (Larchmont) 2003;12:373–80. 13. Chung TK, Lau TK, Yip AS, Chiu HF, Lee DT. Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes. Psychosom Med 2001;63:830–4. 14. Chrousos GP, Torpy DJ, Gold PW. Interactions between the hypothalamic- pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 1998;129:229–40. 15. Paarlberg KM, Vingerhoets AJ, Passchier J, Dekker GA, van Geijn HP. Psychosocial factors and pregnancy outcome: a review with emphasis on methodological issues. J Psychosom Res 1995;39:563–95. 16. Sandman CA, Wadhwa PD, Dunkel-Schetter C, Chicz-DeMet A, Belman J, Porto M, and others. Psychobiological influences of stress and HPA regulation on the human fetus and infant birth outcomes. Ann N Y Acad Sci 1994;739:198–210. 17. Sandman CA, Wadhwa PD, Chicz-DeMet A, Dunkel-Schetter C, Porto M. Maternal stress, HPA activity, and fetal/infant outcome. Ann N Y Acad Sci 1997;814:266–75. 18. Smith R, Cubis J, Brinsmead M, Lewin T, Singh B, Owens P, and others. Mood changes, obstetric experience and alterations in plasma cortisol, beta-endorphin and corticotrophin releasing hormone during pregnancy and the puerperium. J Psychosom Res 1990;34(1):53–69. 19. Wadhwa PD, Dunkel-Schetter C, Chicz-DeMet A, Porto M, Sandman CA. Prenatal psychosocial factors and the neuroendocrine axis in human pregnancy. Psychosom Med 1996;58:432–46. 20. Dorn LD, Susman EJ, Petersen AC. Cortisol reactivity and anxiety and depression in pregnant adolescents: a longitudinal perspective. Psychoneuroendocrinology 1993;18:219–39. 21. Kurki T, Hiilesmaa V, Raitasalo R, Mattila H, Ylikorkala O. Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol 2000;95:487–90. 22. Perkin MR, Bland JM, Peacock JL, Anderson HR. The effect of anxiety and depression during pregnancy on obstetric complications. Br J Obstet Gynaecol 1993;100:629–34. 23. Kent A, Hughes P, Ormerod L, Jones G, Thilaganathan B. Uterine artery resistance and anxiety in the second trimester of pregnancy. Ultrasound Obstet Gynecol 2002;19:177–9. 24. [Anonymous]. American Psychiatric Association: practice guildeline for major depressive disorder in adults. Am J Psychiatry 1993;150(Suppl 1):1–26. 25. [Anonymous]. Health Indicators. Volume 2002, no 1. Depression. Ottawa (ON): Statistics Canada; 2002. Catalogue no 82-221-XIE. 26. Altshuler LL, Cohen LS, Moline ML, Kahn DA, Carpenter D, Docherty JP. The expert consensus guideline series. Treatment of depression in women. Postgrad Med 2001;(Special No):1–107. 27. Angst J, Baastrup P, Grof P, Hippius H, Poldinger W, Weis P. The course of monopolar depression and bipolar psychoses. Psychiatr Neurol Neurochir 1973;76:489–500. 28. Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, and others. Three year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990;47:1093–9. 29. Arck PC. Stress and pregnancy: loss of immune mediators, hormones and neurotransmitters. Am J Reprod Immunol 2001;46:117–23. 30. Erickson MT. The influence of health factors on psychological variables predicting complications of pregnancy, labor and delivery. J Psychosom Res 1976;20(1):21–4. 31. Kelly R, Zatzick D, Anders T. The detection and treatment of psychiatric disorders and substance use among pregnant women cared for in obstetrics. Am J Psychiatry 2001;158:213–9. 32. Lou HC, Hansen D, Nordentoft M, Pryds O, Jensen F, Nim J, and others. Prenatal stressors of human life affect fetal brain development. Dev Med Child Neurol 1994;36:826–32. 33. Orr ST, Miller CA. Maternal depressive symptoms and the risk of poor pregnancy outcome. Review of the literature and preliminary findings. Epidemiol Rev 1995;17:165–71. 34. Steer RA, Scholl TO, Hediger ML, Fischer RL. Self-reported depression and negative pregnancy outcomes. J Clin Epidemiol 1992;45:1093–9. 35. Wadhwa PD, Sandman CA, Porto M, Dunkel-Schetter C, Garite TJ. The association between prenatal stress and infant birth weight and gestational age at birth: a prospective investigation. Am J Obstet Gynecol 1993;169:858–65. 36. Zax M, Sameroff AJ, Babigian HM. Birth outcomes in the offspring of mentally disordered women. Am J Orthopsychiatry 1977;47:218–30. 37. Michel-Wolfromm H. The psychological factor in spontaneous abortion. J Psychosom Res 1968;12(1):67–71. 38. Preti A, Cardascia L, Zen T, Pellizzari P, Marchetti M, Favaretto G, and others. Obstetric complications in patients with depression—a population-based case-control study. J Affect Disord 2000;61:101–6. 39. Teixeira JM, Fisk NM, Glover V. Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study. BMJ 1999;318:153–7. 40. Field T, Diego M, Hernandez-Reif M, Salman F, Schanberg S, Kuhn C, and others. Prenatal anger effects on the fetus and neonate. J Obstet Gynaecol 2002;22:260–6. 41. Hoffman S, Hatch MC. Depressive symptomatology during pregnancy: evidence for an association with decreased fetal growth in pregnancies of lower social class women. Health Psychol 2000;19:535–43. 42. Dayan J, Creveuil C, Herlicoviez M, Herbel C, Baranger E, Savoye C, and others. Role of anxiety and depression in the onset of spontaneous preterm labor. Am J Epidemiol 2002;155:293–301. 43. Orr ST, James SA, Blackmore PC. Maternal prenatal depressive symptoms and spontaneous preterm births among African-American women in Baltimore, Maryland. Am J Epidemiol 2002; 156:797–802. 44. McAnarney ER, Stevens-Simon C. Maternal psychological stress/depression and low birth weight. Is there a relationship? Am J Dis Child 1990;144:789–92. 45. Cohler BJ, Gallant DH, Grunebaum HU, Weiss JL, Gamer E. Pregnancy and birth complications among mentally ill and well mothers and their children. Soc Biol 1975;22:269–78. 46. Weinstock M. Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 2001;65:427–51. 47. Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkins CW. Stress hormone levels of children of depressed mothers. Dev Psychopathol 2002;14:333–49. 48. Mahomed K, Gulmezoglu AM, Nikodem VC, Wolman WL, Chalmers BE, Hofmeyr GJ. Labor experience, maternal mood and cortisol and catecholamine levels in low-risk primiparous women. J Psychosom Obstet Gynaecol 1995;16:181–6. 49. Zuckerman B, Amaro H, Bauchner H, Cabral H. Depressive symptoms during pregnancy: relationship to poor health behaviors. Am J Obstet Gynecol 1989;160:1107–11. 50. Josefsson A, Berg G, Nordin C, Sydsjo G. Prevalence of depressive symptoms in late pregnancy and postpartum. Acta Obstet Gynecol Scand 2001;80:251–5. 51. Evans J, Heron J, Francomb H, Oke S, Golding J. Cohort study of depressed mood during pregnancy and after childbirth. BMJ 2001;323:257–60. 52. Kenyon FE. Termination of pregnancy on psychiatric grounds: a comparative study of 61 cases. Br J Med Psychol 1969;42:243–54. 53. Krener P, Treat JN, Hansen RL. Research in pregnancy and mental illness: testing old wives’ hypotheses. J Psychosom Obstet Gynaecol 1993;14:163–83. 54. Appleby L. Suicide during pregnancy and in the first postnatal year. BMJ 1991;302:137–40. 55. Hirschfeld RM, Keller MB, Panico S, Arons BS, Barlow D, Davidoff F, and others. The National Depressive and Manic-Depressive Association consensus statement on the undertreatment of depression. JAMA 1997;277:333–40. 56. Kleiner GJ, Greston WM. Suicide during pregnancy. In: Cherry SH, Merkatz IR, editors. Complications of pregnancy: medical, surgical, psychosocial and perinatal. Volume 4. 4th ed. Philadelphia (PA): Williams & Wilkins; 1991. p 269–89. 57. Hostetter A, Stowe ZN, Strader JR Jr, McLaughlin E, Llewellyn A. Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications. Depress Anxiety 2000;11(2):51–7. 58. Paarlberg KM, Vingerhoets AJ, Passchier J, Dekker GA, Heinen AG, van Geijn HP. Psychosocial predictors of low birthweight: a prospective study. Br J Obstet Gynaecol 1999;106:834–41. 59. Allister L, Lester BM, Carr S, Liu J. The effects of maternal depression on fetal heart rate response to vibroacoustic stimulation. Dev Neuropsychol 2001;20:639–51. 60. Bergant AM, Reinstadler K, Moncayo HE, Solder E, Heim K, Ulmer H, and others. Spontaneous abortion and psychosomatics. A prospective study on the impact of psychological factors as a cause for recurrent spontaneous abortion. Hum Reprod 1997;12:1106–10. 61. Arck PC, Rose M, Hertwig K, Hagen E, Hildebrandt M, Klapp BF. Stress and immune mediators in miscarriage. Hum Reprod 2001;16:1505–11. 62. Sugiura-Ogasawara M, Furukawa TA, Nakano Y, Hori S, Aoki K, Kitamura T. Depression as a potential causal factor in subsequent miscarriage in recurrent spontaneous aborters. Hum Reprod 2002;17:2580–4. 63. Marcus SM, Barry KL, Flynn HA, Blow FC. [Improving detection, prevention and treatment of depression and substance abuse in childbearing women: critical variables in pregnancy and pre-pregnancy planning, 1998.] Located at University of Michigan Clinical Ventures, Faculty Group Practice. 64. Coverdale JH, Chervenak FA, McCullough LB, Bayer T. Ethically justified clinically comprehensive guidelines for the management of the depressed pregnant patient. Am J Obstet Gynecol 1996;174):169–73. 65. Wisner KL, Gelenberg AJ, Leonard H, Zarin D, Frank E. Pharmacologic treatment of depression during pregnancy. JAMA 1999;282:1264–9. 66. Bosquet M, Egeland B. Associations among maternal depressive symptomatology, state of mind and parent and child behaviors: implications for attachment-based interventions. Attach Hum Dev 2001;3:173–99. 67. O’Connor TG, Heron J, Glover V. Antenatal anxiety predicts child behavioral/emotional problems independently of postnatal depression. J Am Acad Child Adolesc Psychiatry 2002;41:1470–7. 68. Weinberg MK, Tronick EZ. The impact of maternal psychiatric illness on infant development. J Clin Psychiatry 1998;59(Suppl 2):53–61. 69. Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, and others. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002;159:1889–95. 70. Maki P, Veijola J, Rasanen P, Joukamaa M, Valonen P, Jokelainen J, and others. Criminality in the offspring of antenatally depressed mothers: a 33-year follow-up of the Northern Finland 1966 birth cohort. J Affect Disord 2003;74:273–8. 71. Hammen C, Brennan PA. Severity, chronicity, and timing of maternal depression and risk for adolescent offspring diagnoses in a community sample. Arch Gen Psychiatry 2003;60:253–8. Author(s)Manuscript received November 2003, revised, and accepted February 2004. 1. Graduate student, Motherisk Program, The Hospital for Sick Children and the Department of Pharmacology, University of Toronto, Toronto, Ontario. 2. Associate Director, Motherisk Program, The Hospital for Sick Children, Toronto, Ontario. 3. Professor of Psychiatry, McMaster University, Hamiton, Ontario. 4. Director, Motherisk Program, The Hospital for Sick Children, Toronto, Ontario; Professor, the Department of Pharmacology, University of Toronto. Toronto, Ontario; Ivey Chair in Molecular Toxicology, University of Western Ontario, London, Ontario. Address for correspondence: Dr G Koren, The Motherisk Program, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8 e-mail: gkoren@sickkids.ca
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