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Risks of untreated depression during pregnancy
Lori Bonari, Heather Bennett, Adrienne Einarson, RN, Gideon Koren, MD, FRCPC
One of my patients who was taking an antidepressant for major depression is now pregnant and does not wish to take it any more. I believe she needs to continue her medication. She, however, is adamant about stopping it because she believes it would put her baby at risk. Is there evidence that not treating depression during pregnancy puts babies at risk?
A growing body of literature investigating the effects of not treating depression on mother and developing fetus suggests that untreated depression is associated with adverse fetal outcomes and a higher risk of maternal morbidity, including suicide ideation and attempts, and postpartum depression.
L'une de mes patientes qui prend des antidépresseurs pour une dépression profonde est maintenant enceinte et souhaite arrêter sa médication. Je crois qu'elle devrait la continuer. Par ailleurs, elle est déterminée à arrêter parce qu'elle croit que ces médicaments posent des risques pour son enfant. Y a-t-il des données scientifiques démontrant qu'une pharmacothérapie contre la dépression durant la grossesse pose des risques pour l'enfant à venir?
Une quantité grandissante d'ouvrages qui étudient les effets de ne pas traiter la dépression les mères et le foetus en développement font valoir que la dépression non traitée est associée à des issues indésirables chez le foetus et à un risque plus élevé de morbidité chez la mère, notamment l'idée du suicide et les tentatives de suicide ainsi que la dépression postpartale.
It is well known that women of childbearing age often suffer from major depression, which is most prevalent among people between 25 and 44 years old.1 Estimates of lifetime risk in community-derived samples of pregnant women vary between 10% and 25%.1-3 Although commonly used antidepressants have been shown to be safe during pregnancy,4 women sometimes decide to discontinue these drugs when pregnancy is diagnosed out of fear of harming their babies.5
The literature examining risk of untreated depression during pregnancy suggests that psychopathologic symptoms during pregnancy have physiologic consequences for fetuses.6 It has also been postulated that depression results in hazardous behaviours that can indirectly affect obstetric outcomes.
Studies have found that mental illness can affect a mother's functional status and her ability to obtain prenatal care and avoid dangerous behaviour. Mental illness can also affect decision-making capacities by causing cognitive distortions, and, because of this, it has been associated with poor attendance at antenatal clinics and malnutrition (which could lead to low birth weight babies).7
Depressed women are more likely to smoke and to use alcohol or other substances, which might compromise pregnancy. Depressed women can show deteriorating social function, emotional withdrawal, and excessive concern about their future ability to parent. They report excessive worry about pregnancy, are less likely to attend regular obstetric visits, and do not comply with prenatal advice. They take prenatal vitamins less often than nondepressed women and know less about the benefits of folic acid.2,3,8 These behaviours all predict poor pregnancy outcome.
Severe depression also carries the risk of self-injurious, psychotic, impulsive, and harmful behaviours that can affect pregnancy. When patients refuse treatment, physicians should monitor patients for crises, such as suicide attempts, deteriorating social function, psychosis, and inability to comply with obstetric advice.1
Links to adverse outcomes
Untreated depression during pregnancy has been linked to other adverse outcomes, such as spontaneous abortion,9,10 increased uterine artery resistance,11 small head circumference, low ApGAR scores, need for special neonatal care, neonatal growth retardation, preterm delivery, and babies with high cortisol levels at birth.1,2,6-8,12-15 Studies also suggest that pregnant women who are depressed require more operative deliveries and report labour as more painful, which means they require more epidural analgesia.
Gestational hypertension and subsequent preeclampsia has also been linked to untreated depression during pregnancy. Psychopathology during pregnancy is thought to affect the uterine environment and, therefore, could have an effect on fetal outcome. Current theories suggest that depression increases excretion of vasoactive hormones in the mother, and these hormones then mediate birth outcome. More research is needed to find out the exact mechanism.7
It is also evident that the risks of untreated depression do not end with birth. Women with untreated antenatal depression are also at increased risk of postpartum depression.16 Studies have shown that these women are less capable of carrying out maternal duties and of bonding with their children.17
One study found elevated risk of preterm delivery (<37 weeks), low birth weight (<2500 g), and small for gestational age (<10th percentile) babies in women with Beck Depression Inventory (BDI) scores of 21 or more who were not receiving treatment.15 Prenatal stress and depression have also been significantly associated with lower infant birth weight and younger gestational age at birth.18,19 A recent study of lower social class women found that depression was associated with restricted fetal growth and small for gestational age babies.20 There is also a clear association between increased hypothalamic, pituitary, and placental hormones in depressed mothers and the occurrence of preterm labour.21
Studies have investigated the link between depression and preeclampsia. Strenuous work, depression, and anxiety might increase risk of this condition, but the stress of daily living has not been associated with it. In Finland, 623 nulliparous women at low risk of preeclampsia all had healthy first trimesters and were then tested for depression and anxiety at about 12 weeks' gestation. Depression (odds ratio 2.5, 95% confidence interval 1.2 to 5.3) and anxiety were both associated with increased risk of preeclampsia.6
A growing body of literature suggests that the risk of adverse effects of untreated depression in pregnancy is high. Because selective serotonin reuptake inhibitors have been shown to be safe during pregnancy, the risk-benefit ratio is quite clear.
- Wisner KL, Zarin DA, Holmboe ES, Appelbaum PS, Gelenberg AJ, Leonard HL, et al. Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 2000;157(12):1933-40.
- Nonacs R, Cohen LS. Depression during pregnancy: diagnosis and treatment options. J Clin Psychiatry 2002;63(7):24-30.
- Burt VK, Stein K. Epidemiology of depression throughout the female life cycle. J Clin Psychiatry 2002;63(Suppl 7):9-15.
- Addis A, Koren G. Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol Med 2000;30(1):89-94.
- Einarson A, Selby P, Koren G. Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling. J Psychiatry Neurosci 2001;26(1):44-8.
- Kurki T, Hiilesmaa V, Raitasalo R, Mattila H, Ylikorkala O. Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol 2000; 95(4):487-90.
- Evans J, Heron J, Francomb H, Oke S, Golding J. Cohort study of depressed mood during pregnancy and after childbirth. BMJ 2001;323(7307):257-60.
- Zuckerman B, Amaro H, Bauchner H, Cabral H. Depressive symptoms during pregnancy: relationship to poor health behaviors. Am J Obstet Gynecol 1989;160(5 Pt 1):1107-11.
- Arck PC. Pregnancy loss. Am J Reprod Immunol 2001;45:303-9.
- 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(10):2580-4.
- Teixeira JM, Fisk NM, Glover V. Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study. BMJ 1999;318(7177):153-7.
- 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(5):830-4.
- Ashman SB, Dawson G, Panagiotides H, Yamada E, Wilkins CW. Stress hormone levels of children of depressed mothers. Dev Psychopathol 2002;14(2):333-49.
- 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(1):165-71.
- Steer RA, Scholl TO, Hediger ML, Fischer RL. Self-reported depression and negative pregnancy outcomes. J Clin Epidemiol 1992;45(10):1093-9.
- Marcus SM, Flynn HA, Blow FC, Barry KL. J Womens Health. In press.
- 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(2):173-99.
- 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.
- Hostetter A, Szsjjmel A. Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications. Depress Anxiety 2000;11(2):51-7.
- 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(6):535-43.
- Weinstock M. Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 2001;65(5):427-51.
Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Ms Bonari, Ms Bennett, and Ms Einarson are members and Dr Koren is Director of the Motherisk Program. Dr Koren, a Senior Scientist at the Canadian Institutes for Health Research, is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation and, in part, by a grant from the Canadian Institutes for Health Research. This paper was partially based on a study supported by the Ontario Council of Women's Health.