Outcomes of infants exposed to multiple antidepressants during pregnancy: results of a cohort study.

BACKGROUND: A single study has been published documenting an increased risk for adverse pregnancy outcomes following use of more than one antidepressant during pregnancy. OBJECTIVE: To examine whether multiple antidepressant use is associated with increased rates of major malformations, spontaneous abortions (SA), therapeutic abortions (TA), stillbirths, preterm birth, low birth weight, small for gestational age (SGA) and admission to the neonatal intensive care unit (NICU). METHODS: Information from the Motherisk Program's prospectively collected database of 1243 women with gestational exposure to antidepressants. We compared pregnancy outcomes of 89 women exposed to >1 antidepressants, 89 taking one antidepressant, and 89 women not exposed to antidepressants (n= 267). Women were matched for maternal age, smoking and alcohol use. Groups were compared using odds ratios and ANOVA. RESULTS: 11/89 (12%) took 3 and 78 (88%) took 2 antidepressants. There were no statistically significant differences in any of the outcomes analyzed among the 3 groups except for a lower mean gestational age at birth in the multi-antidepressant group (0.9 week, P=0.036). There were 9 admissions to NICU from the antidepressant groups and 3 from the non-exposed group; but this did not reach statistical significance. CONCLUSIONS: There is a small risk of preterm delivery that is associated with exposure to antidepressant therapy, although the clinical relevance remains to be determined.

Adverse effects of antidepressant use in pregnancy: an evaluation of fetal growth and preterm birth.

OBJECTIVE: To compare the rates of low birth weight, preterm delivery and small for gestational age (SGA), in pregnancy outcomes among women who were exposed and nonexposed to antidepressants during pregnancy. METHODS: At The Motherisk Program, we analyzed pregnancy outcomes of 1,243 women in our database who took various antidepressants during their pregnancy. Nine hundred and twenty-eight of these women and 928 nonexposed women who delivered a live born infant were matched for age, (+/-2 years), smoking and alcohol use and specific pregnancy outcomes were compared between the two groups. RESULTS: There were 82 (8.8%) preterm deliveries in the antidepressant group and 50 (5.4%) in the comparison group. OR: 1.7 (95% CI: 1.18-2.45). There were 89 (9.6%) in the antidepressant group and 76 (8.2%) in the comparison group who delivered babies evaluated as SGA; OR: 1.19 (95% CI: 0.86-1.64). The mean birth weight in the antidepressant group was 3,449+/-591 g and 3,455+/-515 g in the comparison group (P=.8). CONCLUSION: The use of antidepressants in pregnancy appears to be associated with a small, but statistically significant increased rate in the incidence of preterm births, confirming results from several other studies. It is difficult to ascertain whether this small increased rate of preterm births is confounded by depression, antidepressants, or both. However, we did not find a statistically significant difference in the incidence of SGA or lower birth weight. This information adds to limited data available in the literature regarding these outcomes following the use of antidepressants in pregnancy.

Existence and severity of nausea and vomiting in pregnancy (NVP) with different partners.

Nausea and vomiting in pregnancy (NVP) is a widespread condition which may impact on the quality of life. Our objective was to understand the role of the placenta, which is mostly made up of fetal cells, in NVP. We examined the relationship between NVP and different partners in the same women. If a paternal contribution to placental function affects NVP, this could shed light on the genetics of the most common condition in pregnancy. We assessed nausea and vomiting in two groups of 100 women counselled by the Motherisk Program in Toronto, using a score from 1 (none) to 5 (severe with hyperemesis). The first group had >/=2 pregnancies with the same partner; the second had >/=2 pregnancies with >/=2 partners. Scores were averaged across pregnancies, partners and overall. Regression was used to separate numbers of pregnancies and partners. The 100 women having one partner reported an average score of 3.1 in their 261 pregnancies, which was similar to the score of 3.0 in 319 multi-partner pregnancies (p = 0.508). There was a positive (but weak) correlation between gravidity and NVP score (Spearman's rho = 0.21, p < 0.001) but not between partner and score. There was a linear increase in scores from 2.7 in the first pregnancy, to 4.0 in the tenth (rho = 0.948, p < 0.01). After controlling for number of pregnancies, number of partners was not associated with NVP scores (p = 0.302). NVP severity tends to increase with each successive pregnancy. Different partners have no impact on NVP severity.

Validation studies of the Pregnancy Unique-Quantification of Emesis (PUQE) scores.

The Pregnancy-Unique Quantification of Emesis (PUQE) is a scoring system to quantify the severity of nausea and vomiting of pregnancy (NVP). Based on quantification of the 3 physical symptoms of NVP (nausea, vomiting and retching), PUQE closely correlates with the validated but much more complex Rhodes' score. We examined the ability of PUQE to predict four independent aspects of NVP: (a) pregnant women's ability to take multivitamins. (b) rates of emergency room visits and hospitalisation for NVP. (c) health cost of NVP. (d) women's self scores of well-being in NVP. Using large prospective cohorts of women for each end point, severity of NVP measured by PUQE had significant predictive value for all 4 aspects sought. PUQE has been validated through 4 independent clinical outcomes of direct importance and relevance for NVP. The simplicity of PUQE and the ease of its execution make it a practical tool for both clinical follow-up and research.

Taking antidepressants during late pregnancy. How should we advise women?

QUESTION: In light of recent negative media attention to antidepressant use during late pregnancy, several of my patients have either discontinued or are considering discontinuing their antidepressant medications. How can I best counsel these patients on taking antidepressants during late pregnancy? ANSWER: Antidepressant use during the third trimester has been associated occasionally with a transient neonatal withdrawal-like syndrome characterized by jitteriness, self-limiting respiratory difficulties, and problems with feeding. When counseling patients, the risk of these adverse effects must be weighed against the risks associated with untreated depression during late pregnancy. Abrupt discontinuation of psychotropic medications has been associated with both physical (eg, withdrawal) and psychological (eg, suicidal thoughts) symptoms.

Use of antidepressants by pregnant women: evaluation of perception of risk, efficacy of evidence based counseling and determinants of decision making.

BACKGROUND: The World Health Organization predicts that by 2012, depression will be the number one disease in the world. Thus, many women who become pregnant will require treatment with antidepressants. We are aware that women and their health care providers remain hesitant to prescribe and take these drugs during pregnancy, despite evidence of the relative safety. OBJECTIVES: 1) To determine perception of risk of antidepressant drugs by pregnant women with depression, 2) to determine the efficacy of evidence-based counseling, and 3) to identify determinants that influence women in their decision making regarding the continuation/discontinuation of antidepressants during pregnancy. METHODS: Women who called The Motherisk Program requesting information about the safety of an antidepressant during pregnancy were compared with two other groups: 1) Women who called about antibiotic use (i.e., non-teratogenic drugs used short-term) and 2) women who called about gastric medications (i.e., non-teratogenic drugs used long-term). Their perception of risk was measured before and after evidenced-based information was given and determinants of decision making was also evaluated. RESULTS: We recruited 100 women taking antidepressants during pregnancy and 100 in each comparison group. Despite receiving evidence-based reassuring information, 15% of antidepressant users, compared to 4% using gastric drugs and 1% using antibiotics, chose to discontinue their medication. The main determinants of decision making were based on: information received prior to calling Motherisk, family and friends advice, the internet, sequence of advice given and if a women was undecided at the time of call. CONCLUSIONS: Women continue to fear taking antidepressants during pregnancy, more so than non psychiatric drugs, however, evidence based counseling can lower this fear, although not totally. Deciding whether to continue to take a medication or not during pregnancy, is a complex decision for women and their healthcare providers to make.

SSRI'S and other antidepressant use during pregnancy and potential neonatal adverse effects: impact of a public health advisory and subsequent reports in the news media.

BACKGROUND: On Aug 9th 2004 Health Canada released an advisory, which followed a similar one from the FDA regarding the use of SSRI's and other antidepressants during pregnancy and potential adverse effects on newborns. In neither advisory was it stated that women should discontinue their antidepressant. In the seven days following the release of this advisory, The Motherisk Program received 49 calls from anxious women in response to the media reporting of this information. OBJECTIVE: To examine the impact of the advisory and subsequent reporting in the media, on the decision-making of women, currently taking an antidepressant, who called The Motherisk Program after becoming aware of this information. METHODS: We attempted to follow up all the women who had called us who were alarmed by this advisory and asked them to complete a specially designed questionnaire. RESULTS: We were able to complete 43/49 (88%) follow-ups of the women who contacted us. All of the callers reported that the messages in the media caused a great deal of anxiety. Seven misunderstood the advisory, ie their children were more than 1 year old, five had discontinued their antidepressant (3 abruptly (2 later restarted after speaking with Motherisk counsellors)and 2 with some form of tapering off) and(6) were considering discontinuation, but decided to continue following reassurance from Motherisk CONCLUSION: Medical information regarding fetal and infant safety, disseminated in the public domain, should be transferred in a way that does not influence a pregnant woman to make decisions that may not be in the best interest of hers or her child's health.

Pregnancy outcome following exposure to permethrin and use of teratogen information.

NIX is a 1% permethrin creme rinse used for the treatment of head lice. There are no studies regarding human exposure during pregnancy. The primary objective of this study was to examine the safety of permethrin exposure during pregnancy. The secondary objective was to examine how teratogen information is perceived and used by women who requested information regarding this product. Women who had called the Motherisk and MotherSafe Programs to inquire about exposure to permethrin during pregnancy were followed-up to ascertain the outcome of their pregnancies. These women were compared with another group who had not been exposed to any known teratogenic drugs. Women who decided not to use permethrin were administered an additional questionnaire. We enrolled 147 women and completed outcomes on 113 pregnancies of women who had used permethrin some time during their pregnancy. There were 106 live births, six spontaneous abortions, one therapeutic abortion, and one major malformation in the women who used permethrin in the first trimester. The mean birthweight was 3540 +/- 492 g and the mean gestational age was 40 +/- 1 weeks. There were no statistically significant differences between the exposed and comparison groups in any of the pregnancy outcomes. Of the 34 women who chose not to use permethrin and who completed the additional questionnaire, 18 (52%) did not use permethrin because they did not feel the information was sufficiently reassuring. The results of this study suggest that the use of permethrin products during pregnancy appears to be relatively safe because there was no increase in the rates of major malformations. We also found that some women will not use a product during pregnancy unless they can receive a 100% guarantee that it will not harm their baby.

Nausea and vomiting in pregnancy: results of a survey that identified interventions used by women to alleviate their symptoms.

Nausea and vomiting of pregnancy (NVP) affects most pregnant women. There are safe and effective treatments available; however, most women choose to avoid pharmacological therapies and try lifestyle and dietary changes to treat their condition. To date, no attempt has been made to quantify women's experience with a variety of interventions. This study aims to identify factors commonly reported by women that alleviate their symptoms of NVP. Five hundred women with NVP, calling a pregnancy healthline between February 1996 and July 1999, completed a questionnaire where they were asked to rate which of 21 factors helped and to what extent each factor helped to improve their NVP symptoms. For each item, the 'frequency' (percentage of women who indicated that item as an improvement) and 'mean importance' (mean importance score of women who indicated that item as an improvement) were multiplied to give the 'overall impact' score. All 500 women reported that dietary and lifestyle changes helped to improve their NVP symptoms. However, most items were rated low and only 31% of women reported benefit from the use of pharmacological treatment. In conclusion, this study has identified that NVP is a multifaceted condition. Lifestyle changes including validation, supportive counseling and dietary adjustments are important components, that can be used to counsel women with NVP, concomitantly with safe and effective treatment.

Effects of antibacterials on the unborn child: what is known and how should this influence prescribing.

Antibacterials are among the most commonly prescribed drugs worldwide. In general, infections occur in pregnant women at much the same rate as in the general population. However, as a result of physiological changes brought about by pregnancy, some infections, such as those of the urinary tract, may have an increased incidence. It is important to remember that almost every drug crosses the placenta, ensuring that the unborn fetus is also exposed. When prescribing an antibacterial agent to a pregnant woman, it is important that the mother is treated appropriately while at the same time protecting the unborn child. Certain factors need to be addressed, such as the possible teratogenic risk, changes in pharmacokinetics and the potential toxicity of the drug. In this paper we have reviewed various classes of antibacterials which are commonly used during pregnancy, including penicillins, beta-lactam inhibitors, cephalosporins, macrolides, aminoglycosides, tetracyclines, lincosamides, fluoroquinolones, sulfonamides, nitrofurans, and anti-tubercular agents. Some of these drugs have been on the market for many years, whereas others are relatively new and increasingly popular, despite the fact that the older drugs remain very effective. After reviewing the evidence-based information from epidemiological studies, it appears that most antibacterial agents can be used relatively safely during pregnancy. Women who are pregnant should not be denied appropriate antibacterial therapy because of a lack of information. It is possible to treat the mother, while protecting the unborn child, by prescribing an agent that the causative bacteria is sensitive to, rather than a perceived 'safer' option that may not effectively treat the infection and which may also add to the growing problem of bacterial resistance.

Postmarketing surveillance for human teratogenicity: a model approach.

BACKGROUND: Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity. METHODS: We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. RESULTS: The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. CONCLUSIONS: As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy.

Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study.

OBJECTIVE: Because there are no studies available on the safety of venlafaxine during pregnancy, the authors' goal in this study was to determine whether venlafaxine increases the risk for major malformations. METHOD: Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. CONCLUSIONS: These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%-3%.

Evidence based information on drug use during pregnancy: a survey of community pharmacists in three countries.

OBJECTIVE: To evaluate whether community pharmacists provide evidence-based information to women inquiring about specific drug use during pregnancy. DESIGN: A trained female student posing as a surrogate shopper requested information about the relative safety/risks of medications during pregnancy in two scenarios. Forty randomly selected pharmacies were surveyed in the Netherlands, Canada and Iceland, and pharmacists' recommendations were noted. Main outcome measures included the type of information that was provided, its presentation, and the source of information used. RESULTS: A relatively small proportion of pharmacists surveyed, provided evidence-based information regarding the drugs in question. Only 14% referred to current medical literature, while 60% consulted the product monograph. Over 90% of pharmacists referred the client to a physician. CONCLUSIONS: Community pharmacists do not disseminate evidence-based recommendations when counseling women on drug use in pregnancy, and need further education on resources concerning drugs in pregnancy that are currently available.

Discontinuing antidepressants and benzodiazepines upon becoming pregnant. Beware of the risks of abrupt discontinuation.

QUESTION: Two of my patients are planning to become pregnant. One is taking paroxetine and the other lorazepam. We have discussed what to do when they become pregnant and have decided they should stop taking these drugs as soon as pregnancy is confirmed. Is this the right decision? ANSWER: The decision to discontinue these drugs during pregnancy should be based on scientific evidence rather than "hearsay" that women should not take psychotropic medications during pregnancy. Recent epidemiologic studies have documented the relative safety of these drugs, so women should not feel compelled to stop taking them when they become pregnant. If, after receiving appropriate evidence-based information, a woman decides to stop taking the drugs, they should be gradually tapered off to avoid abrupt discontinuation syndrome.

Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling.

OBJECTIVE: To assess the consequences to mother and baby of abruptly discontinuing antidepressant or benzodiazepine medication during pregnancy and to assess the impact of our counselling. PARTICIPANTS: All women who consulted the Motherisk Program between November 1996 and December 1997 and who stopped taking antidepressant or benzodiazepine medication when pregnancy was confirmed agreed to participate in the study. DESIGN AND INTERVENTIONS: Subjects were interviewed, received counselling, and completed a questionnaire 1 month after their initial call and after the birth of their baby. RESULTS: Of 36 women who completed the study, 34 discontinued their medication abruptly for fear of harming the fetus, 28 on the advice of their physician; 26 (70.3%) women reported physical and psychological adverse effects, 11 reported psychological effects only, and 11 reported suicidal ideation (4 were admitted to hospital). After counselling, 22 of 36 (61.1%) women resumed taking their medication, and 4 found that they no longer required it. One woman had a therapeutic abortion and 2 experienced spontaneous abortions; there were therefore 35 healthy babies (including 2 sets of twins) born to 33 women; 14 of 21 mothers breast-fed their babies while taking their psychotropic medication, with no adverse effects reported. CONCLUSIONS: When assessing the risks and benefits of taking psychotropic medication during pregnancy, women and their physicians should be aware that the abrupt discontinuation of psychotropic drugs can lead to serious adverse effects. Counselling is effective in reassuring women to adhere to therapy.

The safety of dextromethorphan in pregnancy : results of a controlled study.

BACKGROUND: Dextromethorphan (DM), the d-isomer of the codeine analog levorphanol, is an active ingredient present in a variety of cough and cold remedies. Recently, data generated from a study in chick embryos were extrapolated to suggest that pregnant women should not use this drug because of the risk of birth defects. We conducted a controlled study of pregnant women who used DM, to examine the possible teratogenic risk in humans. MATERIALS AND METHODS: We followed up women who used DM and had been counseled by the Motherisk Program during their pregnancy. A control group of women was matched for age, smoking, alcohol use, and disease state (upper respiratory tract infection, not treated with DM). RESULTS: We were able to ascertain pregnancy outcome in 184 women. There were 172 live births, 10 spontaneous abortions, 1 therapeutic abortion, and 1 stillbirth. One hundred twenty-eight of the women used the drug during the first trimester of pregnancy. There were three major malformations (2.3%) among the babies of women who used DM in the first trimester, seven minor malformations, and the mean (+/- SD) birth weight was 3,381 +/- 670 g. In the control group, there were 174 live births, 8 spontaneous abortions, and 2 therapeutic abortions. There were five major malformations, one of which was a chromosomal abnormality (2.8%), eight minor malformations, and the mean birth weight was 3,446 +/- 571 g. CONCLUSION: This study fails to show that DM use during pregnancy increases the rates of major malformations above the expected baseline rate of 1% to 3%.