Adrienne Einarson

PREVALENCE OF DEPRESSION DURING PREGNANCY: SYSTEMATIC REVIEW

OBJECTIVE: Current estimates of the prevalence of depression during pregnancy vary widely. A more precise estimate is required to identify the level of disease burden and develop strategies for managing depressive disorders. The objective of this study was to estimate the prevalence of depression during pregnancy by trimester, as detected by validated screening instruments (ie, Beck Depression Inventory, Edinburgh Postnatal Depression Score) and structured interviews, and to compare the rates among instruments. DATA SOURCES: Observational studies and surveys were searched in MEDLINE from 1966, CINAHL from 1982, EMBASE from 1980, and HealthSTAR from 1975. METHODS OF STUDY SELECTION: A validated study selection/data extraction form detailed acceptance criteria. Numbers and percentages of depressed patients, by weeks of gestation or trimester, were reported. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data; a third party resolved disagreement. Two raters assessed quality by using a 12-point checklist. A random effects meta-analytic model produced point estimates and 95% confidence intervals (CIs). Heterogeneity was examined with the χ2 test (no systematic bias detected). Funnel plots and Begg-Mazumdar test were used to assess publication bias (none found). Of 714 articles identified, 21 (19,284 patients) met the study criteria. Quality scores averaged 62%. Prevalence rates (95% CIs) were 7.4% (2.2, 12.6), 12.8% (10.7, 14.8), and 12.0% (7.4, 16.7) for the first, second, and third trimesters, respectively. Structured interviews found lower rates than the Beck Depression Inventory but not the Edinburgh Postnatal Depression Scale. CONCLUSION: Rates of depression, especially during the second and third trimesters of pregnancy, are substantial. Clinical and economic studies to estimate maternal and fetal consequences are needed.

Perinatal Risks of Untreated Depression During Pregnancy

Objective: To review the literature on the perinatal risks involved in untreated depression during pregnancy. Method: We searched Medline and medical texts for all studies pertaining to this area up to the end of April 2003. Key phrases entered were depression and pregnancy, depression and pregnancy outcome, and depression and untreated pregnancy. We did not include bipolar depression. Results: While there is wide variability in reported effects, untreated depression during pregnancy appears to carry substantial perinatal risks. These may be direct risks to the fetus and infant or risks secondary to unhealthy maternal behaviours arising from the depression. Recent human data suggest that untreated postpartum depression, not treatment with antidepressants in pregnancy, results in adverse perinatal outcome. Conclusion: The biological dysregulation caused by gestational depression has not received appropriate attention: most studies focus on the potential but unproven risks of psychotropic medication. No in-depth discussion of the role of psychotherapy is available. Because they are not aware of the potentially catastrophic outcome of untreated maternal depression, this imbalance may lead women suffering from depression to fear teratogenic effects and refuse treatment.

Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors

BACKGROUND Antidepressants have been commonly used by women of childbearing age. Recent studies suggest that paroxetine, a selective serotonin reuptake inhibitor (SSRI), might specifically increase teratogenic risk. OBJECTIVES The purpose of this study was to quantify first-trimester exposure to paroxetine and birth defects and examine potential sources of bias in the in utero or postnatal detection of more congenital malformations among women with depression. We also sought to examine whether paroxetine was used for the same indications as other SSRIs among pregnant women. METHODS This meta-analysis was designed to quantify malformation rates associated with the use of paroxetine. A search of the literature from 1985 to 2006 (English language) found in MEDLINE, EMBASE, REPROTOX, Scopus, and Biological Abstracts was conducted using the following terms: pregnancy outcome, congenital or fetal AND anomalies, malformations, cardiac/heart defects, AND selective serotonin reuptake inhibitors, paroxetine, and Paxil. Administrative databases of medication and medical services use in the Province of Quebec, Canada, were used to calculate the rates of ultrasound and echocardiogram in pregnancy and infancy in women/infants exposed to SSRIs and to compare the indications for general SSRI use versus paroxetine use. RESULTS Based on the studies analyzed, first-trimester paroxetine exposure was associated with a significant increase in the risk for cardiac malformation (odds ratio [OR], 1.72; 95% CI, 1.22-2.42). Women using antidepressants in pregnancy had a 30% higher rate of utilization of ultrasound in pregnancy. Infants of women who received SSRIs underwent approximately twice as many echocardiograms in the first year of life compared with children of women who used nothing. Significantly more women receiving paroxetine used the drug for anxiety or panic than women receiving other SSRIs (OR, 4.11; 95% CI, 2.39-7.08). CONCLUSIONS Based on the results of this metaanalysis, first-trimester exposure to paroxetine appears to be associated with a significant increase in the risk for cardiac malformation. However, a detection bias cannot be ruled out as contributing to the apparent increased detection of cardiovascular malformation of children exposed in utero to paroxetine. A significantly greater number of women were using paroxetine for anxiety or panic when compared with women using other SSRIs.

DEPRESSION DURING PREGNANCY : OVERVIEW OF CLINICAL FACTORS

Depression during pregnancy is common, affecting an estimated 20% of women. However, conflicting data exist concerning the outcomes of this disorder. Thus, we reviewed studies that presented evidence for the use of antidepressants and those that examined untreated depression during the gestational period, in terms of clinical and epidemiological aspects.Observational studies have provided reassuring evidence of the safety of antidepressant use during pregnancy. However, due to the reluctance of healthcare providers to prescribe and patients to take medication during the obstetric period, approximately three-quarters of those diagnosed with depression remain untreated. Furthermore, healthcare providers apparently do not recognise the disorder in up to 50% of pregnant women who experience depression. Increased antidepressant dosing during pregnancy may be required to maintain euthymia; however, guidelines for effective dosing levels are absent. Consequently, many patients remain inadequately treated. Substantial maternal and fetal morbidity including substance abuse, functional impairment, increased risk of postnatal depression, and poor pregnancy outcomes have resulted from untreated depression.The consequences of those outcomes are likely to be associated with substantial clinical, social and economic burdens. An incidence-based assessment of the consequences of prenatal depression would be useful in order to: (i) establish the impact on the quality of life of these patients and their families; (ii) assess the associated economic burden on individual families and the healthcare system; and (iii) to provide epidemiological data to enable the provision of suitable management strategies for these patients.

Evaluation of the Risk of Congenital Cardiovascular Defects Associated With Use of Paroxetine During Pregnancy

OBJECTIVE In 2005-2006, several studies noted an increased risk of cardiovascular birth defects associated with maternal use of paroxetine compared with other antidepressants in the same class. In this study, the authors sought to determine whether paroxetine was associated with an increased risk of cardiovascular defects in infants of women exposed to the drug during the first trimester of pregnancy. METHOD From teratology information services around the world, the authors collected prospectively ascertained, unpublished cases of infants exposed to paroxetine early in the first trimester of pregnancy and compared them with an unexposed cohort. The authors also contacted the authors of published database studies on antidepressants as a class to determine how many of the women in those studies had been exposed to paroxetine and the rates of cardiovascular defects in their infants. RESULTS The authors were able to ascertain the outcomes of 1,174 infants from eight services. The rates of cardiac defects in the paroxetine group and in the unexposed group were both 0.7%. The rate in the database studies (2,061 cases from four studies) was 1.5%. CONCLUSIONS Paroxetine does not appear to be associated with an increased risk of cardiovascular defects following use in early pregnancy, as the incidence in more than 3,000 infants was well within the population incidence of approximately 1%.

The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study

Objective  Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations.

Antidepressant Use during Pregnancy and the Rates of Spontaneous Abortions: A Meta-Analysis

BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy. OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates. METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy. RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (χ 2 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes. CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.

Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy.

OBJECTIVES The primary objective of our study was to examine the safety and the secondary objective was to examine the effectiveness of ginger for nausea and vomiting of pregnancy (NVP). STUDY DESIGN Pregnant women who called the Motherisk Program who were taking ginger during the first trimester of pregnancy were enrolled in the study. The women were compared with a group of women who were exposed to nonteratogenic drugs that were not antiemetic medications. The women were followed up to ascertain the outcome of the pregnancy and the health of their infants. They were also asked on a scale of 0 to 10 how effective the ginger was for their symptoms of NVP. RESULTS We were able to ascertain the outcome of 187 pregnancies. There were 181 live births, 2 stillbirths, 3 spontaneous abortions, and 1 therapeutic abortion. The mean birth weight was 3542+/-543 g, the mean gestational age was 39+/-2 weeks, and there were three major malformations. There were no statistical differences in the outcomes between the ginger group and the comparison group with the exception of more infants weighing less than 2500 g in the comparison group (12 vs 3, P < or =.001). There were a total of 66 completed effectiveness scores with the mean score of 3.3+/-2.9 SD. CONCLUSION These results suggest that ginger does not appear to increase the rates of major malformations above the baseline rate of 1% to 3% and that it has a mild effect in the treatment of NVP.

Smoking in pregnancy and lactation: a review of risks and cessation strategies

BackgroundDespite documented evidence of harm to fetus and infant, a substantial number of women continue to smoke during pregnancy and lactation.ObjectiveTo examine the literature regarding smoking during pregnancy and breastfeeding to ascertain adverse effects as well as the efficacy of interventions to enable women to stop smoking in the perinatal period.Study designA comprehensive literature search was undertaken to identify all published studies reporting on smoking in pregnancy and lactation. MEDLINE, EMBASE, PUBMED, and Web of Science databases were searched for studies published in English from 1966 to 2008 that reported on smoking in pregnancy and breastfeeding, with information on adverse effects and on all forms of smoking cessation, including behavioral interventions, nicotine replacement therapy, and pharmacotherapy such as antidepressants.ResultsThere is evidence that smoking in pregnancy and lactation may cause many adverse affects in the perinatal period, childhood, and up to adulthood. These adverse effects include infertility, ectopic pregnancy, spontaneous abortion, placenta insufficiency, low birth weight, fetal growth restriction, preterm delivery, orofacial clefts, SIDS, craniosynostosis, clubfoot, childhood respiratory disease, attention deficit disorder, and some childhood cancers. A number of strategies have been developed to assist pregnant women in quitting smoking, including both behavioral interventions and pharmacological therapies, such as nicotine replacement and antidepressant therapy.ConclusionsBehavioral interventions report only modest success rates. Nicotine replacement therapy and antidepressants appear to be safe to use in pregnancy, but do not achieve a substantially higher success rate for quitting.

Incidence of major malformations in infants following antidepressant exposure in pregnancy: results of a large prospective cohort study.

Objective: To ascertain if antidepressants, as a group, increase the risk for major malformations, as well as assessing each individual antidepressant. Methods: At The Motherisk Program, we analyzed pregnancy outcomes of women (n = 1243) from prospectively collected cases in our database, who were exposed to antidepressants during their pregnancy. We then compared them with a matched comparison group of women (n = 1243) who were not exposed (nonteratogen group). Results: Women (n = 928) who fit the criteria for inclusion, were exposed in the first trimester of pregnancy, and gave birth to a live-born infant were matched to women (n = 928) in the comparison group. There were 30 (3.2%) major malformations in the antidepressant group and 31 (3.3%) in the comparison group (OR 0.9; 95% CI 0.5 to 1.61). The antidepressants included in the analysis were: bupropion (113), citalopram (184), escitalopram (21), fluvoxamine (52), nefazodone (49), paroxetine (148), mirtazepine (68), fluoxetine (61), trazodone (17), venlafaxine (154), and sertraline (61). Conclusions: As a group, antidepressant use in the first trimester of pregnancy is not associated with an increased risk for major malformation above the baseline. In addition, no individual antidepressant was associated with an increased risk of a specific malformation.