Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance

Herbal medicine use during pregnancy in a group of Australian women

BACKGROUND: There are limited data on the extent of women's use of herbal medicines during pregnancy, despite the fact that knowledge of the potential benefits or harms of many of these products is sparse, particularly with respect to their use in pregnancy. We aimed to measure the prevalence of herbal medicine use in a group of pregnant women attending a public tertiary maternity hospital in Melbourne, Australia. Secondary aims were to explore why women took the herbal medicine, where they received advice, what form the supplements took and if they perceived the supplements to be helpful. METHODS: Consecutive pregnant women were approached in the antenatal clinic and the birth centre at around 36–38 weeks gestation. A questionnaire was developed and self-administered in English, as well as being translated into the four most common languages of women attending the hospital: Cantonese, Vietnamese, Turkish and Arabic. Back translation into English was undertaken by different professional translators to verify accuracy of both words and concepts. Data collected included demographic information, model of pregnancy care and herbal supplement use. Descriptive statistics were used initially, with stratified and regression analysis to compare sub-groups. RESULTS: Of 705 eligible women, 588 (83%) agreed to participate. Of these, 88 (15%) completed the questionnaire in a language other than English. Thirty-six percent of women took at least one herbal supplement during the current pregnancy. The most common supplements taken were raspberry leaf (14%), ginger (12%) and chamomile (11%). Women were more likely to take herbal supplements if they were older, tertiary educated, English speaking, non-smokers and primiparous. CONCLUSION: Use of herbal supplements in pregnancy is likely to be relatively high and it is important to ascertain what supplements (if any) women are taking. Pregnancy care providers should be aware of the common herbal supplements used by women, and of the evidence regarding potential benefits or harm

Women’s beliefs about medicines and adherence to pharmacotherapy in pregnancy: Opportunities for community pharmacists?

Background During pregnancy women might weigh benefits of treatment against potential risks to the unborn child. However, non-adherence to necessary treatment can adversely affect both mother and child. To optimize pregnant women’s beliefs and medication adherence, community pharmacists are ideally positioned to play an important role in primary care. Objective This narrative review aimed to summarize the evidence on 1) pregnant women’s beliefs, 2) medication adherence in pregnancy, and 3) community pharmacists’ counselling during pregnancy. Method Three search strategies were used in Medline and Embase to find original studies evaluating women’s beliefs, medication adherence and community pharmacists’ counselling during pregnancy. All original descriptive and analytic epidemiological studies performed in Europe, North America and Australia, written in English and published from 2000 onwards were included. Results We included 14 studies reporting on women’s beliefs, 11 studies on medication adherence and 9 on community pharmacists’ counselling during pregnancy. Women are more reluctant to use medicines during pregnancy and tend to overestimate the teratogenic risk of medicines. Risk perception varies with type of medicine, level of health literacy, education level and occupation. Furthermore, low medication adherence during pregnancy is common. Finally, limited evidence showed current community pharmacists’ counselling is insufficient. Barriers hindering pharmacists are insufficient knowledge and limited access to reliable information. Conclusion Concerns about medication use and non-adherence are widespread among pregnant women. Community pharmacists’ counselling during pregnancy is insufficient. Further education, training and research are required to support community pharmacists in fulfilling all the opportunities they have when counselling pregnant women

Veterinary Considerations for the Theoretical Resurrection of Extinct Species

The de-extinction of the dinosaur is a dubious possibility but its consideration brings forth some issues that are at least worthy of scientific discussion. In this review, we discuss two distinct issues that have implications for a de-extinct species such as a dinosaur: the ability, or lack thereof, to safely sedate a rare and potentially fractious animal capable of harming the veterinary staff tasked with its care; and, disease risks associated with a species that has been extinct for millions of years. To identify potential sedatives, comparative pharmacology will be needed to uncover the links between receptor pharmacology and the desired clinical outcomes of activating established alpha-2 adrenergic, opioid, and benzodiazepine receptors. Specific to disease control, it will be necessary to understand the unique susceptibility of the new species to current diseases as well as predicting their reservoir capacity for potential human and veterinary pandemic diseases. While the topics presented herein are not exhaustive, this review highlights some of the foremost research that should be conducted in order to serve the unique veterinary needs of a de-extinct species using the dinosaur as a paradigm. Addressing these issues should be considered if an intact dinosaur genome becomes available, regardless of the feasibility of dinosaur resurrection

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors

The use of herbal medicines during breastfeeding: A population-based survey in Western Australia

Background: Main concerns for lactating women about medications include the safety of their breastfed infants and the potential effects of medication on quantity and quality of breast milk. While medicine treatments include conventional and complementary medicines, most studies to date have focused on evaluating the safety aspect of conventional medicines. Despite increasing popularity of herbal medicines, there are currently limited data available on the pattern of use and safety of these medicines during breastfeeding. This study aimed to identify the pattern of use of herbal medicines during breastfeeding in Perth, Western Australia, and to identify aspects which require further clinical research. Methods: This study was conducted using a self-administered questionnaire validated through two pilot studies. Participants were 18 years or older, breastfeeding or had breastfed in the past 12 months. Participants were recruited from various community and health centres, and through advertising in newspapers. Simple descriptive statistics were used to summarise the demographic profile and attitudes of respondents, using the SPSS statistical software. Results: A total of 304 questionnaires from eligible participants were returned (27.2% response rate) and analysed. Amongst the respondents, 59.9% took at least one herb for medicinal purposes during breastfeeding, whilst 24.3% reported the use of at least one herb to increase breast milk supply. Most commonly used herbs were fenugreek (18.4%), ginger (11.8%), dong quai (7.9%), chamomile (7.2%), garlic (6.6%) and blessed thistle (5.9%). The majority of participants (70.1%) believed that there was a lack of information resources, whilst 43.4% perceived herbal medicines to be safer than conventional medicines. Only 28.6% of users notified their doctor of their decision to use herbal medicine (s) during breastfeeding; 71.6% had previously refused or avoided conventional medicine treatments due to concerns regarding safety of their breastfed infants. Conclusions: The use of herbal medicines is common amongst breastfeeding women, while information supporting their safety and efficacy is lacking. This study has demonstrated the need for further research into commonly used herbal medicines. Evidence-based information should be available to breastfeeding women who wish to consider use of all medicines, including complementary medicines, to avoid unnecessary cessation of breastfeeding or compromising of pharmacotherapy

Managing hyperemesis gravidarum: a multimodal challenge

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect