RESUMO
Background/Objectives: Gestational hypertensive disorders (GHD) pose significant maternal and fetal health risks during pregnancy. Preconception physical exercise has been associated with a lower incidence of GHD, but insights into the cardiovascular mechanisms remain limited. This study aimed to evaluate the effect of preconception physical exercise on the complete cardiovascular functions of women at risk for GHD in a subsequent pregnancy. Methods: A non-invasive hemodynamics assessment of arteries, veins, and the heart was performed on 40 non-pregnant women at risk for developing GHD in a subsequent pregnancy. Measurements of an electrocardiogram Doppler ultrasound, impedance cardiography and bio-impedance spectrum analysis were taken before and after they engaged in physical exercise (30-50 min, 3×/week, 4-6 months). Results: After a mean physical exercise period of 29.80 weeks, the total peripheral resistance (TPR), diastolic blood pressure and mean arterial pressure decreased in the total study population, without changing cardiac output (CO). However, in 42% (9/21) of women categorized with high or low baseline CO (>P75 or
RESUMO
Introduction: While breastfeeding is recommended, knowledge regarding medicine transfer to human milk and its safety for nursing infants is limited. Only one paper has previously described dimethyl fumarate (DMF) transfer during breastfeeding in two patients at 5 and 6 months postpartum, respectively. The current case report describes maternal pharmacokinetic data of monomethyl fumarate (MMF), the active metabolite of DMF, and infant exposure estimations of MMF at 3 months postpartum. Methods: A 32-year-old Caucasian woman started DMF therapy (120 mg, 2x/day) for multiple sclerosis at 3 months postpartum, after weaning her infant from breastfeeding. On day 99 after birth, the patient collected four milk samples over 24 h after 6 days of treatment at the initial dose. Additionally, a single maternal blood sample was collected to calculate the milk-to-plasma (M/P) ratio. The samples were analyzed using liquid chromatography coupled with the mass spectrometry method. Results: A wide range of measured steady-state concentrations of MMF (5.5-83.5 ng/mL) was observed in human milk samples. Estimated daily infant dosage values for MMF, calculated with 150 and 200 mL/kg/day human milk intake, were 5.76 and 7.68 µg/kg/day, and the relative infant doses were 0.16 and 0.22%. The observed mean M/P ratio was 0.059, similar to the M/P ratio predicted using the empirical Koshimichi model (0.06). Discussion: Combining this case report with the two previously described cases, the estimated infant exposure is low, albeit with relevant intra- and inter-patient variabilities. Research should further focus on infant exposure and safety.
Assuntos
Fumaratos , Leite Humano , Humanos , Leite Humano/química , Feminino , Adulto , Aleitamento Materno , Recém-Nascido , Esclerose Múltipla/tratamento farmacológico , Imunossupressores , Lactente , MaleatosRESUMO
Objective: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Methods: Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). Results: A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. Discussion and Conclusion: The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.
RESUMO
INTRODUCTION: Breastfeeding is beneficial for the health of the mother and child. However, at least 50% of postpartum women need pharmacotherapy, and this number is rising due to the increasing prevalence of chronic diseases and pregnancies at a later age. Making informed decisions on medicine use while breastfeeding is often challenging, considering the extensive information gap on medicine exposure and safety during lactation. This can result in the unnecessary cessation of breastfeeding, the avoidance of pharmacotherapy or the off-label use of medicines. The UmbrelLACT study aims to collect data on human milk transfer of maternal medicines, child exposure and general health outcomes. Additionally, the predictive performance of lactation and paediatric physiologically based pharmacokinetic (PBPK) models, a promising tool to predict medicine exposure in special populations, will be evaluated. METHODS AND ANALYSIS: Each year, we expect to recruit 5-15 breastfeeding mothers using pharmacotherapy via the University Hospitals Leuven, the BELpREG project (pregnancy registry in Belgium) or external health facilities. Each request and compound will be evaluated on relevance (ie, added value to available scientific evidence) and feasibility (including access to analytical assays). Participants will be requested to complete at least one questionnaire on maternal and child's general health and collect human milk samples over 24 hours. Optionally, two maternal and one child's blood samples can be collected. The maternal medicine concentration in human milk will be determined along with the estimation of the medicine intake (eg, daily infant dose and relative infant dose) and systemic exposure of the breastfed child. The predictive performance of PBPK models will be assessed by comparing the observed concentrations in human milk and plasma to the PBPK predictions. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee Research UZ/KU Leuven (internal study number S67204). Results will be published in peer-reviewed journals and presented at (inter)national scientific meetings. TRIAL REGISTRATION NUMBER: NCT06042803.
Assuntos
Aleitamento Materno , Leite Humano , Lactente , Gravidez , Feminino , Humanos , Criança , Lactação , Mães , Período Pós-PartoAssuntos
Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Complicações na Gravidez/tratamento farmacológico , Encéfalo/diagnóstico por imagemRESUMO
Background: The incidence of diabetes mellitus (both pregestational and gestational) is increasing worldwide, and hyperglycemia during pregnancy is associated with adverse pregnancy outcomes. Evidence on the safety and efficacy of metformin during pregnancy has accumulated resulting in an increase in its prescription in many reports. Aims: We aimed to determine the prevalence of antidiabetic drug use (insulins and blood glucose-lowering drugs) before and during pregnancy in Switzerland and the changes therein during pregnancy and over time. Methods: We conducted a descriptive study using Swiss health insurance claims (2012-2019). We established the MAMA cohort by identifying deliveries and estimating the last menstrual period. We identified claims for any antidiabetic medication (ADM), insulins, blood glucose-lowering drugs, and individual substances within each class. We defined three groups of pattern use based on timing of dispensation: (1) dispensation of at least one ADM in the prepregnancy period and in or after trimester 2 (T2) (pregestational diabetes); (2) dispensation for the first time in or after T2 (GDM); and (3) dispensation in the prepregnancy period and no dispensation in or after T2 (discontinuers). Within the pregestational diabetes group, we further defined continuers (dispensation for the same group of ADM) and switchers (different ADM group dispensed in the prepregnancy period and in or after T2). Results: MAMA included 104,098 deliveries with a mean maternal age at delivery of 31.7. Antidiabetic dispensations among pregnancies with pregestational and gestational diabetes increased over time. Insulin was the most dispensed medication for both diseases. Between 2017 and 2019, less than 10% of pregnancies treated for pregestational diabetes continued metformin rather than switching to insulin. Metformin was offered to less than 2% of pregnancies to treat gestational diabetes (2017-2019). Conclusion: Despite its position in the guidelines and the attractive alternative that metformin represents to patients who may encounter barriers with insulin therapy, there was reluctance to prescribe it.
Assuntos
Diabetes Gestacional , Metformina , Gravidez , Feminino , Humanos , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/epidemiologia , Suíça/epidemiologia , Glicemia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Insulina/uso terapêutico , Resultado da Gravidez , GlucoseRESUMO
With COVID-19 vaccination hesitancy at around 50% in the obstetric population, it is critical to identify which women should be addressed and how. Our study aimed to assess COVID-19 vaccination willingness among pregnant and postpartum women in Europe and to investigate associated determinants. This study was a cross-sectional, web-based survey conducted in Belgium, Norway, Switzerland, The Netherlands, and United Kingdom (UK) in June-August 2021. Among 3194 pregnant women, the proportions of women vaccinated or willing to be vaccinated ranged from 80.5% in Belgium to 21.5% in Norway. The associated characteristics were country of residence, chronic illness, history of flu vaccine, trimester of pregnancy, belief that COVID-19 is more severe during pregnancy, and belief that the COVID-19 vaccine is effective and safe during pregnancy. Among 1659 postpartum women, the proportions of women vaccinated or willing to be vaccinated ranged from 86.0% in the UK to 58.6% in Switzerland. The associated determinants were country of residence, chronic illness, history of flu vaccine, breastfeeding, and belief that the COVID-19 vaccine is safe during breastfeeding. Vaccine hesitancy in the obstetric population depends on medical history and especially on the opinion that the vaccine is safe and on the country of residence.
Assuntos
COVID-19 , Vacinas contra Influenza , Gravidez , Humanos , Feminino , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Transversais , Pandemias , VacinaçãoRESUMO
The hormone hepcidin plays an important role in intestinal iron absorption and cellular release. Cord blood hepcidin values reflect fetal hepcidin status, at least at the time of delivery, but are not available for the Belgian population. Therefore, we aimed (1) to provide the first data on cord blood hepcidin levels in a Belgian cohort and (2) to determine variables associated with cord blood hepcidin concentrations. A cross-sectional, observational study was performed at the University Hospital Leuven, Belgium. Cord blood samples were analyzed using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry. Descriptive statistics, Spearman correlation tests, and Mann-Whitney U tests were performed. In total, 61 nonhemolyzed cord blood samples were analyzed. The median hepcidin level was 17.6 µg/L (IQR: 18.1; min-max: 3.9-54.7). A moderate correlation was observed between cord blood hepcidin and cord blood ferritin (r = 0.493) and hemoglobin (r = -0.342). Cord blood hepcidin was also associated with mode of delivery (p = 0.01), with higher hepcidin levels for vaginal deliveries. Nonetheless, larger studies are needed to provide more evidence on the actual clinical value and benefit of cord blood hepcidin measurements.
Assuntos
Sangue Fetal , Hepcidinas , Gravidez , Feminino , Humanos , Bélgica , Sangue Fetal/química , Estudos Transversais , FerroRESUMO
OBJECTIVE: To describe the mental health of perinatal women in five European countries during the third pandemic wave and identify risk factors related to depressive and anxiety symptoms. DESIGN: A cross-sectional, online survey-based study. SETTING: Belgium, Norway, Switzerland, the Netherlands and the UK, 10 June 2021-22 August 2021. PARTICIPANTS: Pregnant and up to 3 months postpartum women, older than 18 years of age. PRIMARY OUTCOME MEASURE: The Edinburgh Depression Scale (EDS) and the Generalised Anxiety Disorder scale (GAD-7) were used to assess mental health status. Univariate and multivariate generalised linear models were performed to identify factors associated with poor mental health. RESULTS: 5210 women participated (including 3411 pregnant and 1799 postpartum women). The prevalence of major depressive symptoms (EDS ≥13) was 16.1% in the pregnancy group and 17.0% in the postpartum . Moderate to severe generalised anxiety symptoms (GAD ≥10) were found among 17.3% of the pregnant and 17.7% of the postpartum women. Risk factors associated with poor mental health included having a pre-existing mental illness, a chronic somatic illness, having had COVID-19 or its symptoms, smoking, unplanned pregnancy and country of residence. Among COVID-19 restrictive measures specific to perinatal care, pregnant and postpartum women were most anxious about not having their partner present at the time of delivery, that their partner had to leave the hospital early and to be separated from their newborn after the delivery. CONCLUSION: Approximately one in six pregnant or postpartum women reported major depression or anxiety symptoms during the third wave of the pandemic. These findings suggest a continued need to monitor depression and anxiety in pregnancy and postpartum populations throughout and in the wake of the pandemic. Tailored support and counselling are essential to reduce the burden of the pandemic on perinatal and infant mental health.
Assuntos
COVID-19 , Depressão Pós-Parto , Transtorno Depressivo Maior , Gravidez , Recém-Nascido , Feminino , Humanos , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Saúde Mental , Depressão/psicologia , Transtorno Depressivo Maior/epidemiologia , Período Pós-Parto/psicologia , Ansiedade/epidemiologia , Gestantes/psicologia , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/diagnósticoRESUMO
Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36-39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56-0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87-1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8-12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed.
Assuntos
Lítio , Bélgica , Feminino , Idade Gestacional , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos RetrospectivosRESUMO
OBJECTIVE: To assess the knowledge and counseling preferences of the public ('individuals') and pharmacy staff ('professionals') in Belgium on emergency contraceptive pills (ECPs). STUDY DESIGN: Cross-sectional study using 2 different anonymous, online surveys (one addressing the public and one professionals). RESULTS: Overall, 1518 individuals and 1118 professionals participated, obtaining a mean knowledge score of 6.3(±1.8)/10 and 5.0(±1.6)/10, respectively. For the public, a lower level of knowledge was found among men, nonhealthcare workers, and low educated individuals with no prior ECP use/purchase. For professionals, a lower level of knowledge was observed among pharmacy-technicians, French-speaking persons, and professionals with ≥5 years of experience and poorly involved in continuous education. CONCLUSIONS: Limited knowledge on ECPs was observed among the public and pharmacy staff in Belgium, underscoring educational and counseling opportunities on ECPs.
Assuntos
Anticoncepção Pós-Coito , Anticoncepcionais Pós-Coito , Farmácia , Bélgica , Anticoncepção Pós-Coito/métodos , Aconselhamento , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
A Teratology Information Service (TIS) does not exist in Belgium yet but will hopefully be established soon. To prepare for this, we aimed to provide insight into the information needs and counseling preferences of the Belgian public and healthcare professionals (HCPs) regarding medication use in pregnancy and breastfeeding. A cross-sectional study using two anonymous, online surveys disseminated via social media, websites, and newsletters addressing Dutch and French-speaking individuals (≥18 years) and licensed HCPs was performed between June and September 2020. Ethics approval and informed consent were obtained. In total, 1508 public survey respondents (98% women) and 702 HCPs participated. Information needs on perinatal medication use were ubiquitous among both groups, and for which they often relied on patient information leaflets or the product information and online fora. Conflicting information on this topic regularly occurs and complicates HCPs' duties. Women and HCPs assigned an important role to a TIS, both in terms of providing evidence-based information (via a website or app) and being accessible to be contacted in case of questions (by phone or via e-mail or chat). In conclusion, a TIS would be warmly welcomed by women and HCPs in Belgium and should ideally be established soon to address current information needs regarding perinatal medication use and to contribute to research in this field.
Assuntos
Teratologia , Bélgica , Aconselhamento , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Serviços de Informação , Masculino , GravidezRESUMO
Introduction: Quantitative information on disposition of maternal medicines in human milk remains a major knowledge gap. This case report presents the clinical and pharmacokinetic data of a single mother-infant pair exposed to bosentan and sildenafil for the treatment of pulmonary arterial hypertension (PAH) during lactation. Case presentation: A 43-year old mother was treated with sildenafil (20 mg, 3x/day) and bosentan (125 mg, 2x/day) for PAH. Her 21-months old infant received breastfeeding in combination with adequate complementary foods. Milk samples were collected over 24 h, at day 637 and 651 after delivery. The observed average steady-state concentrations of sildenafil (2.84 µg/L) and bosentan (49.0 µg/L) in human milk were low. The Daily Infant Dosage ingested by the nursing infant through human milk was 0.02 µg/kg/day for sildenafil and 0.29 µg/kg/day for bosentan at day 637, and 0.03 µg/kg/day and 0.60 µg/kg/day at day 651. The Relative Infant Dose calculated for an exclusively breastfed infant with an estimated milk intake of 150 ml/kg/day, was 0.06% for sildenafil and 0.24% for bosentan. General health outcome of the infant, reported by the mother, was uneventful until the sampling days. Conclusion: Low medicine concentrations were found in human milk expressed 21 months after delivery after maternal intake of 20 mg sildenafil three times daily and 125 mg bosentan twice daily. General health of the nursing infant until sampling was reported as optimal by the mother.
RESUMO
Community pharmacists in Belgium frequently dispense emergency contraceptive pills (ECPs). However, variable and insufficient counseling practices exist across pharmacies, highlighting the need for standardization and quality improvement strategies. The aim of this project was to develop and test an ECP dispensing protocol for pharmacists. An 'experience-based' co-design approach involving academic and practicing pharmacists was applied, followed by a 4-month test period and interviews to assess users' experiences. In total, eight geographically dispersed pharmacies participated. Pharmacists (n = 15) reached a consensus on most items to be included in the protocol, which was subsequently tested in seven pharmacies, with overall 97 registered ECP conversations. Pharmacists considered the protocol complete but felt that not all items should be mentioned/questioned during all conversations. They suggested only subtle modifications to be made prior to delivering a final protocol ready for nationwide distribution. Despite attributing positive effects to having a protocol, no single pharmacist 'actively' used it at-the-counter but used it instead as a 'checklist' after the encounter. Pharmacists found that the paper-based format of the protocol hindered protocol-based dispensing. Future research is needed to provide evidence on the actual benefits of protocol application, as well as to identify factors influencing the implementation of ECP dispensing using a software-integrated protocol.
RESUMO
Information on medication utilization among pregnant and postpartum women during the pandemic is lacking. We described the prevalence and patterns of self-reported medication use among pregnant and postpartum women during the third wave of the pandemic (June-August 2021). An online questionnaire was distributed in five European countries between June-August 2021. Pregnant women or women who had delivered in the three preceding months, and ≥18 years old, could participate. The prevalence of overall medication use, self-medication, and changes in chronic medication use were determined. A total of 2158 women out of 5210 participants (41.4%) used at least one medication. Analgesics (paracetamol), systemic antihistamines (cetirizine), and drugs for gastric disorders (omeprazole) were the three most used classes. Anti-infectives were less prevalent than during pre-pandemic times. Antidepressants and anxiety related medication use remained similar, despite a higher prevalence of these symptoms. Self-medication was reported in 19.4% of women, and 4.1% of chronic medication users reported that they changed a chronic medication on personal initiative due to the pandemic. In conclusion, medication use patterns in our cohort were mostly similar to those of the first COVID-19 wave and the pre-pandemic period. More studies are needed to explore factors associated with self-medication and changes in chronic medication use due to the pandemic in this perinatal population.
Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Adolescente , Ansiedade/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Feminino , Humanos , Pandemias , Parto , Período Pós-Parto , Gravidez , Gestantes , AutorrelatoAssuntos
Aleitamento Materno , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Feminino , Humanos , Lactente , Lactação , Leite Humano , VacinaçãoRESUMO
Although marketing authorisation holders (MAHs) are involved in monitoring medication safety, it was unclear how they experience their role and current monitoring activities in pregnancy. Therefore, a qualitative study using online focus groups with MAHs and the Belgian umbrella organisation of MAHs was conducted in June-July 2021. In total, 38 representatives of nine organisations participated. Overall, participants reported multiple difficulties with data collection, including underreporting, collection of incomplete information, and loss to follow-up. The limited number of high-quality data collected, the unknown denominator and the lack of comparator data complicate MAHs' data processing activities, preventing them to timely provide evidence in the pregnancy label. Three 'conflicts' inherent to the specific position of MAHs were identified explaining the difficulties they experience, i.e., (1) mistrust from patients and healthcare professionals (HCPs); (2) MAHs' legal obligations and regulatory framework; (3) MAHs' position outside the healthcare context. To overcome these barriers, MAHs suggested that data registration should occur in close collaboration with patients and HCPs, organised within the healthcare context and performed by using a user-friendly system. In conclusion, the reported difficulties and underlying conflicts of MAHs highlight the need for more effective, collaborative data collection strategies to generate new evidence on this topic.
Assuntos
Monitoramento de Medicamentos , Pessoal de Saúde , Feminino , Grupos Focais , Humanos , Marketing , Gravidez , Pesquisa QualitativaRESUMO
Insight into the epidemiology of perinatal medication use during the COVID-19 pandemic is scarce. Therefore, a cross-sectional study using an anonymous web survey was performed in Ireland, Norway, Switzerland, The Netherlands, and United Kingdom (UK) to investigate the prevalence and type of medications used by pregnant and breast-feeding women during the first pandemic wave. Factors associated with medication use were estimated by logistic regression. In total, 8378 women participated (i.e., 3666 pregnant and 4712 breastfeeding women). Most responses were collected in Norway (34%) and The Netherlands (28%), followed by Switzerland (19%), Ireland (17%) and UK (2%). Participants were more often professionally active and more often had a higher educational level compared to the general birthing population in each country. Overall, approximately 60% of women reported having used at least 1 medication in the preceding 3 months. Daily and occasional use was reported by 34% and 42% of pregnant and 29% and 44% of breastfeeding women. The most prevalent ATC (Anatomical Therapeutic Chemical) categories were the nervous system, the respiratory system, the alimentary tract/metabolism, and the musculo-skeletal system. Paracetamol, ibuprofen, antacids, and cetirizine were the most frequently used medications. The rate of antibacterial use was lower than previously reported. Having a chronic illness, country, maternal age, SARS-CoV-2 testing, professional status and time since delivery were associated with medication use. In conclusion, perinatal medication use was highly prevalent during the first pandemic wave, underlining the importance of maintaining counseling efforts on medication use, even in times of disrupted healthcare services and/or limited resources.