Risks of untreated depression in pregnancy.

QUESTION: In my family practice, I tell my female patients of reproductive age who have depression that untreated depression in pregnancy might be more harmful than the unproven risks of antidepressants. However, I recently read in a national news magazine that there is actually no evidence for this advice. Have I missed something? ANSWER: You did not miss anything, so you should continue to advise your pregnant patients as before. News magazines can have substantial bias, as the reporters often only interview "experts" who support their beliefs, as was probably the case in this article. Most glaringly, in this instance, no perinatal psychiatrists were interviewed and none of the experts were clinically involved with pregnant women. We believe that media statements like the one you mentioned might lead women to abruptly discontinue their antidepressants, putting themselves at risk of relapse, hospitalization, and even suicide. Your balancing role in providing your patient with evidence-based information is critical.

Antidepressant use during pregnancy: navigating the sea of information.

QUESTION: When some of my patients who are taking antidepressants learn they are pregnant, they become anxious and confront me with the following statement: "I need this medication, but have heard so many conflicting stories from my friends and on the Internet and in the media that I am not sure if I should continue taking it." How do I advise them, as I have also seen conflicting evidence in the scientific literature? ANSWER: To date, antidepressants are the most studied drugs during pregnancy, with more than 30 000 outcomes examining increased risks of adverse effects on exposed infants. The results of the studies can appear to be conflicting owing to differing interpretation of statistical analysis and subsequent knowledge transfer and translation of the information. However, there does not appear to be a clinically significant increased risk of any of the adverse outcomes reported in peer-reviewed published studies that would preclude a woman from taking a needed antidepressant during pregnancy.

Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study.

Results of previous studies on the safety of antidepressants during pregnancy have been conflicting. The primary objective of this study was to investigate whether first-trimester exposure to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), was associated with increased risk of congenital malformations. The secondary objective was to examine the effects of exposure to antidepressants during pregnancy on birth weight and gestational age.We included 63,395 women from the Norwegian Mother and Child Cohort Study. The women had completed 2 self-administered questionnaires at gestational weeks 17 and 30 on medication use and medical, sociodemographic, and psychological factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry of Norway.Of the 63,395 women, 699 (1.1%) reported using antidepressants during pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first trimester was not associated with increased risk of congenital malformations in general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81-1.84) or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67-3.43). Exposure to antidepressants during pregnancy was not associated with increased risk of preterm birth (adjusted OR, 1.21; 95% CI, 0.87-1.69) or low birth weight (adjusted OR, 0.62; 95% CI, 0.33-1.16).This study does not suggest a strongly increased risk of malformations, preterm birth, or low birth weight following prenatal exposure to antidepressants. Without adjustments for level of maternal depression and various sociodemographic and lifestyle factors, antidepressant use during pregnancy would wrongly have been associated with an increased risk of preterm birth.

Public preferences for counseling regarding antidepressant use during pregnancy: a discrete choice experiment.

BACKGROUND: Counseling about medication safety during pregnancy is delivered inconsistently. The objectives were to determine public preferences and willingness to pay (WTP) for attributes of counseling regarding antidepressant use during pregnancy. Attributes reflected counseling via a telephone Teratology Information Service (TIS) or a visit to a general practitioner (GP). METHODS: A discrete choice survey was conducted with volunteers recruited from the general public. Stated preferences and WTP for teratology counseling were described by six attributes: training of information provider (IP), method of contact, knowing the IP, confidence in the IP, helpfulness of information, and cost. Interactions of preferences with participant characteristics were examined. RESULTS: Of 175 participants, 85% were women and 91% had some college or university education. All attributes had a significant effect on choice. The most important attribute was the helpfulness of information received (WTP C$59 for very helpful information). Counseling via telephone by a trained specialist was preferred, as in a TIS. It was preferred, however, to speak with a provider known to the user (WTP C$43) which is common in a GP setting. Maximum willingness to pay for very helpful information was less for respondents with less education. Respondents who stated that an antidepressant exposure would make them anxious about the pregnancy were willing to pay more for all attributes. CONCLUSIONS: The results suggest that TIS is the preferred model for counseling regarding to antidepressant use during pregnancy. The public valued information that was helpful and preferred receiving information in nontraditional formats; however, familiarity with the provider was important.

Negative impact of non-evidence-based information received by women taking antidepressants during pregnancy from health care providers and others.

OBJECTIVES: The use of antidepressants by women during pregnancy continues to be a controversial subject, with conflicting information regarding the safety of this group of drugs. We sought (1) to determine the impact of information, advice, and comments women received from health care providers, family, and media about use of antidepressants during pregnancy, and (2) to compare experiences regarding the psychosocial impact of women who continued and discontinued antidepressant therapy during pregnancy. METHODS: Women who had taken an antidepressant at some point during pregnancy were interviewed. The responses of women who continued antidepressant therapy throughout pregnancy were compared with those of women who discontinued therapy at some point in the pregnancy. A questionnaire with questions pertaining to information women had received from various individuals regarding the use of an antidepressant while pregnant was administered to both groups. RESULTS: Ninety-four interviews were completed; 78 were with women who continued antidepressant therapy throughout pregnancy, and 16 were with women who discontinued therapy. The small number of women in the discontinuation group was a result of many women declining to participate. More than one half of the women who continued the medication throughout pregnancy had frequently considered discontinuing, despite reassurance that continuation would cause no harm to their baby. Negative information was recalled far more often than reassuring information. CONCLUSION: Information from friends, family, and health care providers can have a negative impact on decision-making regarding pharmacotherapy for depression during pregnancy. Health care providers should be cognizant of this when counselling patients who require antidepressant therapy during pregnancy.

Reliability and validity of the 4-item perceived stress scale among pregnant women: results from the OTIS antidepressants study.

We aimed to estimate the reliability of the 4-item Perceived Stress Scale (PSS) and its validity in predicting maternal depression and quality of life (QoL). Data regarding stress, depression and QoL were collected during pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. The 4-item PSS demonstrated acceptable internal consistency (Cronbach's alpha coefficient = .79), alternate forms stability reliability with the 10-item PSS (Pearson correlation coefficient r = .63; p < .001), convergent validity with the Edinburgh Postnatal Depression Scale (r = .67; p < .001), and concurrent validity with the mental health component of the Short-Form-12 (r = -.62; p < .001) as a measure of QoL. The 4-item PSS is a valid and useful tool for assessing maternal stress during pregnancy.

Human papillomavirus vaccine and pregnancy.

UNLABELLED: QUESTION A: patient of mine who recently learned she was 6 weeks pregnant had received the recombinant human papillomavirus (HPV) quadrivalent vaccine at 4 weeks of gestation. She is quite worried about how this will affect her baby. What is known about the safety of the HPV vaccine during pregnancy? ANSWER: The HPV vaccine is generally not recommended for use in pregnant women. However, theoretically, because it is not a live vaccine, it is not expected to be associated with an increased risk. Also, information from the manufacturer's pregnancy registry and phase 3 clinical trials does not indicate an increased risk of fetal malformations or other adverse effects due to the vaccine.

Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic.

OBJECTIVE: The objective of this study was to report the outcomes of intrauterine pregnancies misdiagnosed as ectopic and exposed to methotrexate, a major teratogen. STUDY DESIGN: We report the outcomes of all subjects who sought consultation after exposure to high-dose methotrexate to induce abortion in presumed ectopic pregnancies, which were later identified as viable intrauterine pregnancies by 3 North American Teratology Information Services between 2002 and 2010. RESULTS: Eight women with normal, desired pregnancies were administered high-dose methotrexate in the first trimester because of presumed, misdiagnosed ectopic pregnancies. All pregnancies resulted in catastrophic outcomes. Two pregnancies resulted in severely malformed newborns with methotrexate embryopathy; 3 women miscarried shortly after exposure, and in 3 the erroneous diagnosis led the physicians to advise and perform surgical termination. CONCLUSION: Erroneous diagnosis of intrauterine pregnancies as ectopic with subsequent first-trimester exposure to methotrexate may result in the birth of severely malformed babies or fetal demise.

Knowledge transfer and translation: examining how teratogen information is disseminated.

BACKGROUND: Well-executed knowledge transfer and translation (KT) has become a vital part of effective health management. Following the thalidomide disaster, women and their health care providers became fearful of medications and environmental exposures that could affect the health of the unborn child. Therefore, it is important to disseminate evidenced-based information to pregnant women and their health care providers, enabling them to make empowered decisions regarding exposures during pregnancy. OBJECTIVES: The objectives were twofold: (1) to explore the knowledge transfer process of teratology information from the research community to health care providers, pregnant women, and the general public; and (2) to examine how this impacts pregnant women and their health care providers who require this information. METHODS: We searched the peer reviewed literature (PUBMED, MEDLINE, and EMBASE), retrieved and examined original studies and review articles, and identified relevant data to evaluate how KT is conducted in this field. RESULTS: We found that KT and teratology information is very complex, with confusing information, over-estimated fears of teratogenicity, as well as unhelpful, often negatively biased information from the media. Of all the methods we identified, Teratogen Information Services (TIS) appears to conduct the most effective KT approaches in this field. CONCLUSION: It is evident that KT in this area needs improvement. Women and their health care providers are highly impacted by the type of teratology information they receive, affecting for example, deciding to terminate a wanted pregnancy or discontinue a needed pharmacotherapy. When disseminating information in this very sensitive and complex field, it is imperative that good KT strategies are used, encompassing the availability and appropriate interpretation of information. It is most important that an evidence-based decision is made to ensure the optimal outcome for both the mother and her unborn child.

Nausea and vomiting of pregnancy (NVP) and depression: cause or effect?

BACKGROUND: Both nausea and vomiting and depression are common conditions affecting women during pregnancy. Several studies have linked depression with nausea and vomiting of pregnancy (NVP); however, researchers were unable to determine whether depression was caused by NVP or by a pre-existing condition. OBJECTIVE: To determine whether NVP is associated with depression in women with no history of depression prior to pregnancy. STUDY DESIGN AND METHODS: This was a prospective, observational, longitudinal study. Women with no diagnosis of depression who contacted The Motherisk Program prior to becoming pregnant or were at < 6 weeks gestation were enrolled in the study. Each woman was interviewed at 8, 11, 18, 30 weeks gestation and at 6-18 weeks post-partum. At each interview, we administered the EDPS, Wellbeing and PUQE questionnaires and analyzed the data for correlation between depression and NVP. RESULTS: Data were analyzed obtained from 57 women. There were five EPDS scores ≥13 (one at baseline and two each at weeks 8 and 11) considered indicative of depression and 11 cases with PUQE scores ≥7, indicative of moderate-high severity of NVP. We did not find an association between high PUQE scores and high EPDS scores and conversely, there was no relationship between high EPDS scores and high PUQE scores. CONCLUSION: No association between depressive symptoms and NVP was observed; however, our sample size was very small and further studies could be done with a larger population of pregnant women.

Perception of teratogenic risk and the rated likelihood of pregnancy termination: association with maternal depression.

OBJECTIVE: Women are often exposed to various medications and medical conditions during pregnancy. Unrealistically high maternal teratogenic risk perception, related to these exposures, may lead to abrupt discontinuation of therapy and (or) termination of a wanted pregnancy. The association between maternal depression and the teratogenic risk perception has not been studied, nor were the actions resulting from this perception. Our objectives were to explore the association between maternal depression, teratogenic risk perception, and the rated likelihood to terminate pregnancy. Additionally, we evaluated possible benefits of counselling. METHODS: We administered the Edinburgh Postnatal Depression Scale (EPDS) to all women who attended the Motherisk Clinic between October 2007 and April 2010. A visual analogue scale was used to determine maternal risk perception in relation to the specific exposure, and the rated likelihood to terminate the pregnancy, before and after counselling. RESULTS: We analyzed data from 413 women. Maternal teratogenic risk perception and the rated likelihood to terminate the pregnancy were significantly lower following counselling. An EPDS score of 13 or more was significantly associated with a higher rated likelihood to terminate the pregnancy (P = 0.03). In a multivariable regression analysis, an EPDS score of 13 or more was found to be an independent predictor of a higher personal teratogenic risk perception (P = 0.03). CONCLUSIONS: Both maternal depression and exposure-directed counselling are associated with maternal risk perception and the rated likelihood to terminate pregnancy. Appropriate counselling may reduce fear of teratogenicity and the likelihood of pregnancy termination.

Primary care physician's attitudes and practices regarding antidepressant use during pregnancy: a survey of two countries.

Little is known about the practices of primary care physicians regarding the prescribing of antidepressants during pregnancy. An anonymous survey was administered to a group of nonrandomly selected Australian general practitioners (n = 61 out of 77) and randomly selected Canadian family physicians (n = 35 out of 111). Responses to a hypothetical scenario and questions regarding beliefs about the use of antidepressant medication during pregnancy were collected. Physicians from both countries feel strongly that antidepressant use during pregnancy is a decision complicated by conflicting reports of safety and risk.

Stigma and attitudes towards antenatal depression and antidepressant use during pregnancy in healthcare students.

Depression in pregnancy or antenatal depression (AD) occurs in approximately one in five women, with potentially deleterious effects to the mother and fetus. People are encouraged to get treatment for depression; however, pregnant women can experience stigma when they reach out for help with depression. Research indicates that healthcare professionals hold stigma against patients who experience mental health conditions, including depression. The public, as well as healthcare professionals may have negative attitudes towards antidepressant use during pregnancy, despite evidence that many antidepressants are relatively safe for use in pregnancy. The objective of this project was to determine what knowledge and opinions healthcare students may hold towards antenatal depression and its treatment, and whether further knowledge and experience lessened the stigma. Medical, pharmacy, and nursing students (n = 309) were given a scenario regarding a woman with AD based on Corrigan's Attribution Questionnaire and asked seven questions based on the scenario that assessed their level of stigma and questions related to treatment. Each student group demonstrated some stigma towards the woman and all groups lacked knowledge regarding treatment of AD. Overall, the nursing students were the most stigmatizing of the three groups. The study demonstrates that healthcare students hold stigma towards people with mental health problems, including pregnant depressed women. It points to a need to increase education about antenatal depression and its treatment.

Pregnant women's perception of risk with use of the H1N1 vaccine.

OBJECTIVE: During the H1N1 influenza pandemic in 2009, The Motherisk Program, a counselling service providing teratology information, received many calls from pregnant women inquiring about the safety of the H1N1 vaccine. We wished to explore pregnant women's perception of risk and the factors associated with deciding whether or not to receive the vaccine. METHODS: Pregnant women who called Motherisk between October 1 and November 30, 2009, requesting counselling regarding the safety of the H1N1 vaccine, and who had not yet received the vaccine, were contacted for follow-up using a structured questionnaire. RESULTS: One hundred thirty women completed the questionnaire; 104 (80%) had received the H1N1 vaccination following their call to Motherisk, and 26 (20%) had not. More than 70% of the women cited confusing and frightening information in the media as a trigger for their concern, prompting them to call Motherisk. Sixty percent stated that information from their primary health care providers or Motherisk contributed to their decision making. CONCLUSION: The H1N1 vaccination rate in pregnant women who contacted Motherisk was higher than the rate in the general population, as many followed Motherisk's recommendation to receive the vaccine. During this period, the media appeared to provide pregnant women with confusing information. In any future pandemic scare, accessibility to primary health care providers or specialized information services such as Motherisk will be key to providing guidance for pregnant women.

H1N1 and influenza viruses: why pregnant women might be hesitant to be vaccinated.

QUESTION: I have been encouraging pregnant women to receive both the H1N1 and influenza vaccines since I became aware of Health Canada's guidelines. However, some of the women in my practice have heard conflicting information, often from media sources, and they are hesitant to be vaccinated. What is the evidence behind these guidelines, and should I really be convincing these women to be vaccinated? ANSWER: Pregnant women and growing fetuses are considered a population vulnerable to H1N1 and influenza viruses. Health Canada published a report in late 2010 estimating that this population was at increased risk of hospitalization and severe outcomes of H1N1 infection. Recommendations included pregnant women as a priority group to receive the H1N1 vaccine as well as the influenza vaccine. This information should be explained unambiguously to pregnant women, and they should be made aware of the sensationalism of media reports, which are often based on opinion and not evidence.

Are probiotics safe for use during pregnancy and lactation?

QUESTION: There has been a great deal of discussion in both the medical and lay literature about the use of probiotics to improve general health. Subsequently, pregnant women have been asking me if probiotics used for treating conditions such as bacterial vaginosis and diarrhea are safe to use during pregnancy and lactation. ANSWER: Current data suggest that probiotic supplementation is rarely systemically absorbed when used by healthy individuals. One meta-analysis and several randomized controlled trials conducted with women during the third trimester of pregnancy did not report an increase in adverse fetal outcomes. There have been no published studies addressing Saccharomyces species use in pregnancy. Probiotics are unlikely to be transferred into breast milk.

Safety of skin care products during pregnancy.

QUESTION: Many of my female patients complain about acne, unwanted hair growth, and other skin problems that have only developed since they became pregnant. Are products used for these types of benign skin conditions safe to use in pregnancy, as it is understandable that women want to look their best at this important time in their lives? ANSWER: With the exception of hydroquinone, which has a relatively high systemic absorption rate, and tretinoin, for which the evidence is controversial, these products act locally and therefore produce minimal systemic levels. Consequently, in most cases women can deal with these cosmetically unappealing skin conditions without compromising the safety of their unborn children.

Prophylactic use of antimalarials during pregnancy.

QUESTION: Some of my pregnant patients wish to travel to malaria-endemic regions. Are there medications that can be used safely during pregnancy for malaria prophylaxis? ANSWER: Pregnant women should avoid travel to malaria-endemic areas if possible. However, if travel cannot be avoided, measures to prevent mosquito bites, along with an effective chemoprophylaxis regimen, should be implemented. Chloroquine or hydroxychloroquine are considered safe to use in all trimesters of pregnancy. Mefloquine is the agent of choice for chloroquine-resistant areas, and evidence suggests it is not associated with an increased risk to the fetus. Although the atovaquone-proguanil drug combination is not currently recommended for use during pregnancy, limited data suggest that it is not harmful to the fetus. Doxycycline and primaquine are not recommended during pregnancy.

Vaccination during pregnancy.

QUESTION: One of my patients is studying to become a dental hygienist. Owing to the program requirements, she received several vaccinations last week, including measles-mumps-rubella, varicella, and hepatitis B (HB) vaccines, as well as a tetanus booster. However, today a blood test confirmed that she is currently 6 weeks pregnant. What is known about the safety of these vaccines during pregnancy, and are there any general recommendations for vaccines for women who are planning to become pregnant or who are currently pregnant? ANSWER: The combination measles-mumps-rubella vaccine and the varicella vaccine are live attenuated vaccines, and are contraindicated during pregnancy owing to theoretical concerns. However, there is no evidence that there are increased risks of malformations, congenital rubella syndrome, or varicella syndrome attributable to these vaccines. The HB and tetanus vaccines are composed of noninfectious particles or toxoids, and theoretically should cause no increased risk to the developing fetus. In addition, limited observational data also support no increased risk of any adverse pregnancy outcomes; consequently, administration of the HB and tetanus vaccines might be, if indicated, considered during pregnancy.