Prescription retinoid and contraception use in women in Australia: A population-based study.

BACKGROUND/OBECTIVES: Oral retinoids are teratogenic, and pregnancy avoidance is an important part of retinoid prescribing. Australia does not have a standardised pregnancy prevention programme for women using oral retinoids, and the contraception strategies for women who use oral retinoids are not well understood. The objectives were to determine trends in the use of prescription retinoids among Australian reproductive-aged women and whether women dispensed oral retinoids used contraception concomitantly. METHODS: This was a population-based study using Australian Pharmaceutical Benefits (PBS) dispensing claims for a random 10% sample of 15-44-year-old Australian women, 2013 - 2021. We described rates and annual trends in dispensing claims for PBS-listed retinoids and contraceptives. We also estimated concomitant oral retinoid and contraceptive use on the day of each retinoid dispensing and determined if there was a period of contraceptive treatment that overlapped. Estimates were then extrapolated to the national level. RESULTS: There were 1,545,800 retinoid dispensings to reproductive-aged women; 57.1% were oral retinoids. The rate of retinoid dispensing to reproductive-aged women increased annually, from 28 dispensings per 1000 population in 2013 to 41 per 1000 in 2021. The rate of oral retinoid dispensing doubled over the study period, from 14 dispensings per 1000 population in 2013 to 28 per 1000 in 2021, while topical retinoid dispensing did not change. Only 25% of oral retinoid dispensings had evidence of concomitant contraceptive use in 2021. CONCLUSIONS: Rates of oral retinoid dispensing have doubled among reproductive-aged women over the past decade. A large percentage of oral retinoid use does not appear to have concomitant contraception use, posing a risk of teratogenic effects in pregnancies.

Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding.

OBJECTIVE: Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD. DESIGN: A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported. RESULTS: Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary. CONCLUSION: These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

Health professionals' role in the transfer of mosaic embryos after preimplantation genetic testing for aneuploidies.

RESEARCH QUESTION: What are health professionals' clinical practices, views and self-rated competencies regarding the transfer of mosaic embryos? DESIGN: This was a cross-sectional study using surveys. RESULTS: Data were collected from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and the Fertility Society of Australia and New Zealand. Ninety-five responses were analysed and reported. The results show that most health professionals (n = 62) discussed the transfer of mosaic embryos for different reasons and raised concerns regarding various risks. Although many health professionals were unsure whether mosaic embryos should be transferred, they were more inclined to encourage transfer if the scenario involved segmental losses compared with mosaicism involving duplication of the entire chromosome (i.e. trisomy 21) (e.g. OR = 0.21, P < 0.001; OR = 2.78, P = 0.04). The majority of health professionals would inform patients about the mosaicism to facilitate informed decision making. The factor that health professionals identified as most important when discussing the transfer of mosaic embryos was the specific chromosome involved. Different self-rated competencies were found among health professionals with different backgrounds. Geneticists and genetic counsellors had the highest self-rated competencies. CONCLUSIONS: Most health professionals were willing to discuss the mosaicism in the embryo with patients to facilitate informed decision making. However, health professionals' uncertainty towards the transfer of mosaic embryos indicated a lack of a standardized transfer policy. In addition, obstetricians, gynaecologists and those with multiprofessional backgrounds showed deficiencies in several self-rated competencies, suggesting that education targeted to these groups is needed to optimize the quality of care of women considering transfer of mosaic embryos.

Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

OBJECTIVE: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. METHOD: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. RESULTS: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. CONCLUSION: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.

Factors influencing patients' decision-making about preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: What are the roles of individual and interpersonal factors in couples' decision-making regarding preimplantation genetic testing for monogenic disorders (PGT-M)? SUMMARY ANSWER: Couples' decision-making regarding PGT-M was associated with individual and interpersonal factors, that is the perceived consistency of information received, satisfaction with information, self-efficacy (individuals' beliefs in their ability to make decisions), actual knowledge about PGT-M and social support from the partner. WHAT IS KNOWN ALREADY: Various factors have been shown to be associated with decision-making regarding PGT-M. However, PGT-M is experienced at an individual level, and to date, no studies have investigated the roles of the above-mentioned individual and interpersonal factors. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study with 279 participants. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups from May 2020 to November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women who had undergone or were considering PGT-M and their partners. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups to complete online questionnaires. Decisional regret, decisional satisfaction and decisional conflict were measured as outcome variables. Multiple linear regressions were performed to examine the association between factors and outcome variables. Mann-Whitney U tests were performed to test the differences between participants who had undergone PGT-M and those who were considering PGT-M. MAIN RESULTS AND THE ROLE OF CHANCE: For couples who had undergone PGT-M, decisional regret was significantly negatively associated with perceived consistency of information received (ß = -0.26, P < 0.01), self-efficacy (ß = -0.25, P < 0.01) and actual knowledge about PGT-M (ß = -0.30, P < 0.001), while decisional satisfaction had positive association with satisfaction with information received (ß = 0.37, P < 0.001) and self-efficacy (ß = 0.24, P < 0.05). For couples who were considering PGT-M, decisional conflict was negatively associated with satisfaction with information received (ß = -0.56, P < 0.001). For females who had undergone PGT-M, decisional regret was negatively associated with social support from the partner (ß = -0.35, P < 0.05) in addition to perceived consistency of information received (ß = -0.24, P < 0.05). In this group, decisional satisfaction was positively associated with women's satisfaction with the information received (ß = 0.34, P < 0.01), social support from the partner (ß = 0.26, P < 0.05) and self-efficacy (ß = 0.25, P < 0.05). For females who were considering PGT-M, decisional conflict was negatively associated with satisfaction with the information received (ß = -0.43, P < 0.01) and social support from the partner (ß = -0.30, P < 0.05). This study also identified those aspects of PGT-M that couples felt most concerned about in relation to their decision-making, in particular safety issues such as short- or long-term health problems for the baby and potential harms to the embryos and the mother's health. The likelihood of getting pregnant and having a baby with a genetic condition being tested for were also important in couples' decision-making. LIMITATIONS, REASONS FOR CAUTION: This study assessed the concerns of couples about having a baby with a variety of genetic conditions. However, condition-specific issues might not be covered. Furthermore, social support from the partner was assessed among females only. Male participants' perceived social support from their partner and the association between mutual support and decision-making were not assessed due to the absence of dyadic data. WIDER IMPLICATIONS OF THE FINDINGS: Results highlight the importance of effective patient education on PGT-M and the need to provide high-quality and consistent information in the context of patient-centred care. Patients are likely to benefit from information that addresses their specific concerns in relation to PGT-M. From females' perspective, support from partners is essential, and partners should, therefore, be encouraged to participate in all stages of the decision-making process. Suggestions for future studies were made. STUDY FUNDING/COMPETING INTEREST(S): B.M. was funded through a Senior Research Fellowship Level B (ID 1078523) from the National Health and Medical Research Council of Australia. L.C. was supported by a University International Postgraduate Award under the Australian Government Research Training Program (RTP) scholarship. No other funding was received for this study. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Decisional needs of patients considering preimplantation genetic testing: a systematic review.

This systematic review reports on the needs and sources of support in patients' decision-making regarding the uptake of preimplantation genetic testing (PGT). Five databases were searched systematically to capture qualitative and quantitative studies. A total of 2336 studies were screened by title and abstract. Twelve studies met the eligibility criteria and reported on 4047 participants. This systematic review shows that patients need information directly relevant to PGT treatment, and information on health care relating to treatment and alternative reproductive options. Information that is too detailed, excessive and contains a large volume of medical terminology can be a barrier to decision-making. Published research suggests that health professionals provide general information on PGT and discuss it in detail only when patients require more information about it. Additionally, studies have shown that patients receive decisional support through mass media, significant persons in their lives and health professionals, whereas referring obstetricians and gynaecologists provided relatively less help compared with other health professionals. This systematic review highlights the importance of developing decision aids that meet patients' decisional needs as indicated in previous studies and that use innovative formats to deliver information. Additionally, given rapid technical developments, a dearth of continuing professional education is available on PGT for clinicians to keep updated.

Pregnancy outcome following first-trimester exposure to fingolimod: A collaborative ENTIS study.

This prospective multicentre cohort study investigated pregnancy outcomes after fingolimod use for multiple sclerosis during pregnancy. Pregnancy outcomes of 63 fingolimod and 62 interferon-ß-exposed pregnancies were compared. Rates of major congenital anomalies (MCA) were 4.8% (2/42) in the fingolimod group versus 2.3% (1/44) in the interferon-ß group (odds ratio, 2.2; 95% confidence interval, 0.2-24.6). The adjusted hazard ratio for spontaneous abortion in fingolimod versus interferon-ß-exposed pregnancies was 0.6 (95% confidence interval, 0.2-1.8). Further studies are needed to definitely rule out a moderately increased MCA risk after fingolimod exposure during pregnancy.

Medications used disproportionately during pregnancy: Priorities for research on the risks and benefits of medications when used during pregnancy.

PURPOSE: To identify medications used disproportionately more or less among pregnant women relative to women of childbearing age. METHODS: Medication use among pregnant women in New South Wales, Australia was identified using linked perinatal and pharmaceutical dispensing data from 2006 to 2012. Medication use in women of childbearing age (including pregnant women) was identified using pharmaceutical dispensing data for a 10% random sample of the Australian population. Pregnant social security beneficiaries (n = 111 612) were age-matched (1:3) to female social security beneficiaries in the 10% sample. For each medication, the risk it was dispensed during pregnancy relative to being dispensed during an equivalent time period among matched controls was computed. Medications were mapped to Australian pregnancy risk categories. RESULTS: Of the 181 included medications, 35 were statistically significantly more commonly dispensed to pregnant women than control women. Of these, 23 are categorised as posing no increased risk to the foetus. Among medications suspected of causing harm or having insufficient safety data, the strongest associations were observed for hydralazine, ondansetron, dalteparin sodium and ranitidine. Use was less likely during pregnancy than control periods for 127 medications, with the strongest associations observed for hormonal contraceptives and progestogens. CONCLUSIONS: Most medications found to be used disproportionately more by pregnant women are indicated for pregnancy-related problems. A large number of medications were used disproportionately less among pregnant women, where avoidance of some of these medications may pose a greater risk of harm. For many other medications avoided during pregnancy, current data are insufficient to inform this risk-benefit assessment.

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor.

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).

An update on maternal medication-related embryopathies.

There is a general perception that any exposure to medication during pregnancy poses a potential risk to the fetus. Most available data about teratogenic drugs is derived from animal studies, case reports, or cohort studies. As a result, counseling women and their partners about the safety of drugs during pregnancy can be difficult due to limited information about efficacy, pharmacokinetics, and teratogenicity of some drugs. However, this should always be done in the context of weighing up potential teratogenic risks with the perinatal risks of an untreated medical or psychiatric condition. Ideally, this counseling should occur prior to a planned pregnancy so that medications and treatment of chronic medical conditions can be optimized. It is important that clinicians providing antenatal care are able to confidently manage women including utilizing appropriate resources. This paper aims at reviewing a selected (non-exhaustive) list of the most commonly prescribed medications considered significant human teratogens and provides recommendations for pre-conception and antenatal counseling.

Utilisation of a NSW teratology information service by pharmacists and patients referred by a pharmacist from 2000 to 2018.

BACKGROUND: MotherSafe is a free telephone counselling service for exposures during pregnancy and breastfeeding. As the last health professional seen prior to consumption of medicines, community pharmacists' opinions on the use of medications in pregnancy/breastfeeding is likely to be particularly sought by women presenting in pharmacies. However, a recent qualitative study revealed that community pharmacists feel unsupported in their role as medicine information providers to pregnant/breastfeeding women. AIM: The aim of the current study was to undertake a descriptive analysis of calls made by pharmacists or pharmacist-referred patients to MotherSafe across the time period 2000-2018. MATERIALS AND METHODS: A retrospective, descriptive study was conducted of call data from January 2000 to December 2018. Aggregate data were examined by type of caller, reason for call, pregnancy category and exposure type. RESULTS: Most calls (57%) related to pregnancy or breastfeeding (39%) with calls equally distributed throughout gestation. Calls regarding potential pregnancy exposures to uncategorised drugs were the most frequent (mainly complementary medicines). Unlike pharmacists, calls from pregnant consumers referred by pharmacists were also frequently regarding category A drugs. CONCLUSIONS: This study highlights the need for reliable evidence-based information sources regarding the use of prescribed medications, over-the-counter and complementary preparations during pregnancy and breastfeeding. There is a need for better education of pharmacists about appropriate information sources and the need to use evidence-based resources other than the A-X categories to advise their clients about the safety or otherwise of medications in pregnancy and breastfeeding.

Medication Use and Pain Management in Pregnancy: A Critical Review.

BACKGROUND: Pain during pregnancy is common, and its management is complex. Certain analgesics may increase the risk for adverse fetal and pregnancy outcomes, while poorly managed pain can result in adverse maternal outcomes such as depression and hypertension. Guidelines to assist clinicians in assessing risks and benefits of exposure to analgesics for the mother and unborn infant are lacking, necessitating evidence-based recommendations for managing pain in pregnancy. METHODS: A comprehensive literature search was conducted to assess pregnancy safety data for pharmacological and nonpharmacological pain management methods. Relevant clinical trials and observational studies were identified using multiple medical databases, and included studies were evaluated for quality and possible biases. RESULTS: Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are appropriate for mild to moderate pain, but NSAIDs should be avoided in the third trimester due to established risks. Short courses of weaker opioids are generally safe in pregnancy, although neonatal abstinence syndrome must be monitored following third trimester exposure. Limited safety data for pregabalin and gabapentin indicate that these are unlikely to be major teratogens, and tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors have limited but overall reassuring safety data. Many of the included studies were limited by methodological issues. CONCLUSIONS: Findings from this review can guide clinicians in their decision to prescribe analgesics for pregnant women. Treatment should be tailored to the lowest therapeutic dose and shortest possible duration, and management should involve a discussion of risks and benefits and monitoring for response. Further research is required to better understand the safety profile of various analgesics in pregnancy.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

Psoriasis in those planning a family, pregnant or breast-feeding. The Australasian Psoriasis Collaboration.

The Australasian Psoriasis Collaboration has reviewed the evidence for managing moderate to severe psoriasis in those who are pregnant or are breast-feeding, or planning a family. The severity of the psoriasis, associated comorbidities and specific anti-psoriasis treatment, along with other exposures, can have a deleterious effect on pregnancy outcomes. Psoriasis itself increases the risk of preterm and low birthweight babies, along with spontaneous and induced abortions, but no specific birth defects have been otherwise demonstrated. The baseline risk for a live born baby to have a major birth defect is 3%, and significant neuro-developmental problem is 5%. In Australia, pregnant women with psoriasis are more likely to be overweight or obese, depressed, or smoke in their first trimester, and are also less likely to take prenatal vitamins or supplements. Preconception counselling to improve maternal, pregnancy and baby health is therefore strongly encouraged. The topical and systemic therapies commonly used in psoriasis are each discussed separately, with regards to pregnancy exposure, breast-feeding and effects on male fertility and mutagenicity. The systemic therapies included are acitretin, adalimumab, apremilast, certolizumab, ciclosporin, etanercept, infliximab, ixekizumab, methotrexate, NBUVB, prednisone, PUVA, secukinumab and ustekinumab. The topical therapies include dithranol (anthralin), calcipotriol, coal tar, corticosteroids (weak, potent and super-potent), moisturisers, salicylic acid, tacrolimus, and tazarotene. As a general recommendation, effective drugs that have been widely used for years are preferable to newer alternatives with less foetal safety data. It is equally important to evaluate the risks of not treating, as severe untreated disease may negatively impact both mother and the foetus.

Phone calls to an Australian pregnancy and lactation counselling service regarding use of galactagogues during lactation - the MotherSafe experience.

Galactagogues represent substances used to enhance breast milk production. Between 2001 and 2014 we identified 2034 phone calls regarding the use of galactagogues made to MotherSafe. The majority involved discussion of domperidone (n = 1884; 92.6%), with the remainder relating to metoclopramide (n = 153; 7.5%) or other herbal galactagogues (eg fenugreek, milk thistle; n = 262; 12.9%). A 50% decrease in total calls occurred from 2011 to 2014, while the percentage of calls regarding herbal galactagogues increased from 0% in 2001 to 23% in 2014. These findings support the need for more robust research surrounding the use of galactagogues in clinical practice.

Counselling regarding paternal exposures: Can we do better?

BACKGROUND: MotherSafe is a free telephone-based counselling service for the general public and healthcare providers concerned about exposures during pregnancy and breastfeeding. Calls relating to paternal exposures are less common, but can cause distress to the person concerned. This review seeks to identify the key concerns and what information is available to address these concerns. AIMS: To review calls made to MotherSafe about paternal exposures to teratogens during the 16 year period, 2000-2015, and to document any patterns or changes in calls over the period. MATERIALS AND METHODS: A retrospective descriptive assessment of a prospectively collected database (2000-2015) was undertaken. Telephone counselling records identified the drugs of concern regarding paternal exposures. The information about paternal exposures provided in consumer and production information was also reviewed. RESULTS: Of a total of 253 103 calls received at MotherSafe between 2000 and 2015, 1072 calls (0.4%) were regarding paternal exposures. The majority of these calls related to immunomodifiers (19%), hair loss products (11%) and antidepressant medications. CONCLUSIONS: Paternal exposures represent a small proportion of all the counselling calls made to MotherSafe. The study highlighted the deficient and often misleading information about paternal exposures found in most consumer and product information sheets or via the internet. The study indicates the important role of Teratogen Information Services like Mothersafe in providing evidence-based information to both consumers and healthcare providers.

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study.

AIMS: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. METHODS: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. RESULTS: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. CONCLUSIONS: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.

Patterns and factors associated with low adherence to psychotropic medications during pregnancy--a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation.

JAK2-V617F is central to the pathogenesis of myeloproliferative neoplasms. We examined whether lestaurtinib decreased JAK2-V617F allele burden and evaluated its clinical benefits and tolerability in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). This phase 2, open-label, multicentre study was designed to detect ≥15% reduction in JAK2-V617F allele burden in 15% of patients. Eligible patients received lestaurtinib 80 mg twice daily for 18 weeks and could participate in a 1-year extension phase of treatment. Of 39 enrolled patients, 27 (69%) had PV; 12 (31%) had ET. While the pre-specified responder rate of 15% was not met, lestaurtinib modestly reduced JAK2-V617F allele burden and reduced spleen size in a subset of patients. Of 37 patients in the full efficacy analysis, 5 (14%) responded clinically. Every patient had ≥1 adverse event, most commonly gastrointestinal (95%). Fifteen patients (38%) experienced serious adverse events; 23 (59%) withdrew due to adverse events. This is the first reported study of JAK2-inhibitor treatment in patients with PV/ET and highlights both the need for further studies to assess the role of JAK2 inhibition in treatment of PV/ET and the use of JAK2-V617F as a biomarker for response. This trial was registered at www.clinicaltrials.gov as NCT00586651.