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1.
BMJ ; 368: m331, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075790

RESUMO

OBJECTIVE: To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. DESIGN: Population based cohort study. SETTING: The UK Clinical Practice Research Datalink. PARTICIPANTS: The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. MAIN OUTCOME MEASURES: Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. RESULTS: Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. CONCLUSIONS: Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. TRIAL REGISTRATION: ClinicalTrials.gov NCT03948620.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Antibacterianos/efeitos adversos , Macrolídeos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Anormalidades Induzidas por Medicamentos/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Anormalidades Cardiovasculares/induzido quimicamente , Anormalidades Cardiovasculares/epidemiologia , Paralisia Cerebral/induzido quimicamente , Paralisia Cerebral/epidemiologia , Estudos de Coortes , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Epilepsia/induzido quimicamente , Epilepsia/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Primeiro Trimestre da Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Reino Unido/epidemiologia
2.
Toxicol Lett ; 324: 1-11, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32035120

RESUMO

α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This study investigated developmental toxicity of α-asarone in zebrafish, especially the cardiotoxicity. Zebrafish embryos were exposed to different concentrations of α-asarone (1, 3, 5, 10, and 30 µM). Developmental toxicity assessments revealed that α-asarone did not markedly affect mortality and hatching rate. In contrast, there was a concentration-dependent increase in malformation rate of zebrafish treated with α-asarone. The most representative cardiac defects were increased heart malformation rate, pericardial edema areas, sinus venosus-bulbus arteriosus distance, and decreased heart rate. Notably, we found that α-asarone impaired the cardiac function of zebrafish by prolonging the mean QTc duration and causing T-wave abnormalities. The expressions of cardiac development-related key transcriptional regulators tbx5, nkx2.5, hand2, and gata5 were all changed under α-asarone exposure. Further investigation addressing the mechanism indicated that α-asarone triggered apoptosis mainly in the heart region of zebrafish. Moreover, the elevated expression of puma, cyto C, afap1, caspase 3, and caspase 9 in treated zebrafish suggested that mitochondrial apoptosis is likely to be the main reason for α-asarone induced cardiotoxicity. These findings revealed the cardiac developmental toxicity of α-asarone, expanding our knowledge about the toxic effect of α-asarone on living organisms.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anisóis/toxicidade , Apoptose/efeitos dos fármacos , Eletrocardiografia/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Cardiotoxicidade/etiologia , Embrião não Mamífero/efeitos dos fármacos , Mitocôndrias Cardíacas/patologia , Peixe-Zebra
3.
BMJ ; 368: m237, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075794

RESUMO

OBJECTIVE: To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine. DESIGN: Cohort study nested in the Medicaid Analytic eXtract for 2004-13. SETTING: Publicly insured pregnancies in the United States. PARTICIPANTS: Pregnant women 18 to 55 years of age and their liveborn infants. INTERVENTIONS: Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy. MAIN OUTCOME MEASURES: Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage. RESULTS: Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses. CONCLUSIONS: On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient. TRIAL REGISTRATION: EUPAS 15946.


Assuntos
Cloridrato de Duloxetina/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez/epidemiologia , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Adolescente , Adulto , Estudos de Coortes , Cloridrato de Duloxetina/uso terapêutico , Feminino , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/epidemiologia , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Pessoa de Meia-Idade , Hemorragia Pós-Parto/induzido quimicamente , Hemorragia Pós-Parto/epidemiologia , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Estados Unidos/epidemiologia , Adulto Jovem
5.
J Ethnopharmacol ; 245: 112180, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31445135

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Anastatica hierochuntica (A. hierochuntica) is a plant consumed in folk medicine for the treatment of reproductive system related problems and metabolic disorders. It is of concern that the herb is commonly consumed by pregnant women towards the end of pregnancy to ease the process of labour, despite the lack of studies evaluating its safety. AIM OF THIS STUDY: This study aimed to investigate the potential toxicity effects of A. hierochuntica in pregnant Sprague-Dawley rats and their developing foetuses. MATERIALS AND METHODS: Experiments were conducted in accordance to the Organisation for Economic Co-operation and Development guideline 414. Animals were randomly divided into four groups (n = 10 females per group): negative control (received the vehicle only), experimental animals received 250, 500, and 1000 mg/kg A. hierochuntica aqueous extracts (AHAE), respectively. Treatment was administered daily by oral gavage from gestational day (GD) 6-20, and caesarian section performed on GD21. RESULTS: There were significant reduction in the corrected maternal weight gain of dams and body weight of foetuses in the lowest and highest dose of AHAE-treated animals compared to the control. These findings were associated with the increase in anogenital distance index and multiple congenital anomalies observed in some of the offspring. On the other hand, rats treated with 500 mg/kg showed higher embryonic survival rate with absence of significant treatment-related effect. CONCLUSION: Findings showed that highest and lowest doses of AHAE have prenatal toxicity effects in SD rats. Therefore, AHAE is potentially harmful to the developing foetuses especially when consumed during the period of implantation and organogenesis. As for the rats treated with 500 mg/kg AHAE, there was no significant treatment-related effect. Hence, we postulate that this finding suggests that the disruption on the hormonal regulation could have been compensated by negative feedback response. The compensated effects of AHAE at 500 mg/kg and the presence of lowest observed adverse effect level (LOAEL) at 250 mg/kg has resulted in a non-monotonous dose response curve (NMDRC), which complicates the determination of the value of no-observed-adverse effect level (NOAEL).


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Múltiplas/induzido quimicamente , Brassicaceae , Desenvolvimento Fetal/efeitos dos fármacos , Extratos Vegetais/toxicidade , Animais , Implantação do Embrião , Feminino , Masculino , Gravidez , Ratos Sprague-Dawley
6.
S Afr Med J ; 109(6): 415-420, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31266560

RESUMO

BACKGROUND: Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively. OBJECTIVES: To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin. METHODS: A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic. RESULTS: Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment. CONCLUSIONS: Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.


Assuntos
Anormalidades Induzidas por Medicamentos/prevenção & controle , Anticoagulantes/efeitos adversos , Conhecimentos, Atitudes e Prática em Saúde , Varfarina/efeitos adversos , Anormalidades Induzidas por Medicamentos/etiologia , Adolescente , Adulto , Atitude Frente a Saúde , Barreiras de Comunicação , Comportamento Contraceptivo , Embolia/prevenção & controle , Serviços de Planejamento Familiar , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Gravidez , Trombose Venosa/tratamento farmacológico , Adulto Jovem
7.
Psychiatr Pol ; 53(2): 223-244, 2019 Apr 30.
Artigo em Inglês, Polonês | MEDLINE | ID: mdl-31317955

RESUMO

OBJECTIVES: Antiepileptic drugs (AEDs), which are commonly used as a treatment for acute phases and prevention of relapses in bipolar disorder (BD) and schizoaffective disorder (SAD), have been often associated to adverse outcomes in pregnancy and major congenital malformations (MCM). We aimed to summarize available evidence assessing these outcomes when AEDs are used in pregnant women with BD and/or SAD. METHODS: We searched four databases from inception to 18 January, 2019. We included peer-reviewed observational studies on the use of AEDs in pregnant women with BD or SAD. We excluded studies not reporting data on BD or SAD, not specifying the AED or not assessing pregnancy outcomes or MCM. RESULTS: The pooled records amounted to 2,861. After duplicate removal and inclusion/exclusion criteria application, we included 9 observational studies assessing patients with BD and SAD. The AEDs evaluated were lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPR) and gabapentin (GBP). VPA and CBZ were the AED most commonly associated to MCM. LTG showed the best safety profile. Higher rates of complications during pregnancy were observed in treated and untreated women with BD compared to healthy controls. CONCLUSIONS: AEDs may produce adverse outcomes in pregnancy and MCM in children of pregnant women with BD or SAD, showing higher risks at higher doses. LTG could be considered in this type of patients, given the low rate of adverse events. VPA and CBZ use should be avoided during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Transtornos Psicóticos/tratamento farmacológico , Adulto , Transtorno Bipolar/tratamento farmacológico , Carbamazepina/efeitos adversos , Feminino , Humanos , Lactente , Gravidez , Resultado da Gravidez
8.
Clin Perinatol ; 46(2): 203-213, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010556

RESUMO

Many conditions that require frequent medication use are common during pregnancy. The purpose of this article is to list some of the most common of these disorders and to discuss the risk to the developing fetus of the medications used most frequently to treat them. Included are drugs used for the treatment of asthma, nausea and vomiting, hyperthyroidism, pain and fever, and depression during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Congênitas/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/prevenção & controle , Acetaminofen/efeitos adversos , Acetaminofen/uso terapêutico , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Agonistas Adrenérgicos beta/efeitos adversos , Agonistas Adrenérgicos beta/uso terapêutico , Analgésicos não Entorpecentes/efeitos adversos , Analgésicos não Entorpecentes/uso terapêutico , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Antieméticos/efeitos adversos , Antieméticos/uso terapêutico , Antitireóideos/efeitos adversos , Antitireóideos/uso terapêutico , Asma/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Feminino , Humanos , Hipertireoidismo/tratamento farmacológico , Antagonistas de Leucotrienos/efeitos adversos , Antagonistas de Leucotrienos/uso terapêutico , Troca Materno-Fetal , Metimazol/uso terapêutico , Êmese Gravídica/tratamento farmacológico , Ondansetron/uso terapêutico , Gravidez , Propiltiouracila/uso terapêutico , Teratogênios
10.
Pediatrics ; 143(4)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30837294

RESUMO

OBJECTIVES: Although teratogenic medications are commonly used to treat rheumatic disease, no standard model currently exists for educating adolescent patients about teratogenic risk or performing routine pregnancy screening. We performed a quality improvement project to increase education and pregnancy screening in girls and women of childbearing age prescribed teratogenic medications in our pediatric rheumatology clinic. METHODS: Eligible participants included female patients age 10 and older prescribed teratogenic medications in a single-center tertiary care pediatric rheumatology clinic. Seven plan-do-study-act cycles were completed to test the following interventions: visible project reminders, physician and nurse education, progress updates, previsit planning, and development of an electronic health record education template. Chart reviews were performed, and control charts were created for each aim to analyze improvement over time. RESULTS: At baseline, 57 of 231 (24.7%) clinic encounters of female patients age 10 years and older taking teratogenic medications had education documented within the last 12 months, and 47 of 231 (20.3%) had pregnancy screening performed at the visit. Implementation of our interventions resulted in improvement in documentation of annual teratogen education (904 of 1135; 79.6%) and routine pregnancy screening (940 of 1135; 82.8%), both of which were statistically significant (P < .0001). Control charts revealed special cause with sustained improvement over >1 year. CONCLUSIONS: The interventions made through this quality improvement project increased the frequency of both teratogen education and urine pregnancy screening in patients taking teratogenic medications. Development of a standardized education template in the electronic health record played a key role in sustaining these improvements over time.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Antirreumáticos/efeitos adversos , Monitorização Fisiológica/métodos , Educação de Pacientes como Assunto/métodos , Doenças Reumáticas/tratamento farmacológico , Teratogênios/análise , Anormalidades Induzidas por Medicamentos/prevenção & controle , Adolescente , Assistência Ambulatorial/métodos , Antirreumáticos/uso terapêutico , Criança , Estudos de Coortes , Prescrições de Medicamentos/estatística & dados numéricos , Registros Eletrônicos de Saúde , Feminino , Hospitais Pediátricos , Humanos , Seleção de Pacientes , Gravidez , Prognóstico , Doenças Reumáticas/diagnóstico , Medição de Risco , Centros de Atenção Terciária , Estados Unidos
11.
Australas Psychiatry ; 27(2): 125-128, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30763123

RESUMO

OBJECTIVES: To describe prescription of sodium valproate (SV) for bipolar mood disorder to potentially child-bearing women within one public mental health service and describe risks of fetal exposure, and safe prescribing practices among psychiatrists. METHODS: A 24-month retrospective chart review with descriptive analysis; narrative review of literature and guidelines. RESULTS: Review of 383 charts demonstrated prescription of valproate to 20% of 98 women aged 15-45, with little evidence of advice regarding risk and contraception. Robust evidence of teratogenic and neurodevelopmental risk underpins increased regulation, and recommendations that valproate not be prescribed to this cohort. CONCLUSIONS: The significant risks associated with SV oblige all prescribers to proactively access authoritative guidelines such as those published by the Centre of Perinatal Excellence.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Padrões de Prática Médica , Complicações na Gravidez/tratamento farmacológico , Teratogênios , Ácido Valproico/uso terapêutico , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Epilepsia/tratamento farmacológico , Feminino , Humanos , Gravidez , Complicações na Gravidez/psicologia , Fatores de Risco , Ácido Valproico/efeitos adversos
12.
Toxicol Ind Health ; 35(1): 63-78, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30803421

RESUMO

The present study aimed to investigate the impact of perinatal potassium bromate (KBrO3) exposure on the development of sensorimotor reflexes and redox status, and on the histological architecture of the brain, liver, and kidney of newborn mice. Pregnant mice received 1-ml bottled drinking water daily by oral intubation and served as the control group. Another group of pregnant mice were supplemented orally with 200 mg/kg body weight KBrO3 dissolved in drinking water from gestation day 5 to postnatal day 21. KBrO3 induced a decrease in the postnatal body weight in the newborn mice. KBrO3-exposed newborn mice showed poor performance and delayed development of the sensorimotor reflexes. Histological changes, increased lipid peroxidation, and altered antioxidants were reported in the cerebrum, cerebellum, medulla oblongata, liver, and kidney of the KBrO3-exposed newborn mice. In conclusion, these findings demonstrated that perinatal exposure to bromate induced oxidative stress, histological and behavioral alterations, and was a potential teratogen in newborn mice.


Assuntos
Bromatos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Anormalidades Induzidas por Medicamentos/etiologia , Anormalidades Induzidas por Medicamentos/patologia , Animais , Animais Recém-Nascidos/anormalidades , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Feminino , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Gravidez , Reflexo de Endireitamento/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Superóxido Dismutase/metabolismo
14.
J Oncol Pharm Pract ; 25(3): 699-702, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29207935

RESUMO

Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities. To our knowledge, this is the first reported case of fetal cardiovascular defects in an infant born to a woman on dasatinib during a twin pregnancy and supports current recommendations to avoid this medication during pregnancy. We also review relevant preclinical and clinical studies of tyrosine kinase inhibitor use during pregnancy and explore alternative therapeutic options for patients with chronic myeloid leukemia during pregnancy to aid clinicians in the appropriate management of these patients so as to minimize both maternal and fetal risks.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Dasatinibe/efeitos adversos , Doenças em Gêmeos/induzido quimicamente , Cardiopatias Congênitas/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez
16.
Congenit Anom (Kyoto) ; 59(2): 39-42, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29653020

RESUMO

To investigate the abnormalities that are specific to administration of flucytosine at one time point during embryonic organogenesis, flucytosine was administered orally to pregnant Sprague Dawley (SD) rats in a single dose on day 11 of pregnancy at 25 or 35 mg/kg. Fetuses on day 20 of pregnancy were externally, viscerally, and skeletally examined. Maternal body weight gain and food consumption were suppressed the day after administration of a 35 mg/kg. Fetal examinations revealed various alterations in both dose groups: externally preaxial polydactyly in the hind limb; skeletally fused lumbar centrum, absent sacral centrum, supernumerary sacral vertebra, and absent ribs. Our findings indicated that specific types of external and skeletal anomalies were induced following flucytosine administration on day 11 of pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Ectromelia/patologia , Desenvolvimento Fetal/efeitos dos fármacos , Flucitosina/toxicidade , Polidactilia/patologia , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Administração Oral , Animais , Esquema de Medicação , Ingestão de Alimentos/efeitos dos fármacos , Ectromelia/induzido quimicamente , Feminino , Feto , Membro Posterior/anormalidades , Membro Posterior/efeitos dos fármacos , Região Lombossacral/anormalidades , Masculino , Exposição Materna/efeitos adversos , Organogênese/efeitos dos fármacos , Polidactilia/induzido quimicamente , Gravidez , Ratos , Ratos Sprague-Dawley , Costelas/anormalidades , Costelas/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
17.
Skeletal Radiol ; 48(4): 517-525, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30341712

RESUMO

BACKGROUND: Following the thalidomide disaster (1958-62), Henkel and Willert analysed the pattern of dysmelia in the long bones (J Bone Joint Surg Br. 51:399-414, 1969) and the extremities, Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970). Willert's material from deformed extremities is re-examined here asking "How does thalidomide reduce the skeleton?" MATERIALS AND METHODS: We reviewed the original data collection of Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), comprising musculoskeletal histology slides from 30 children affected by thalidomide with radiographs of hands (19 cases) and feet (4 cases). RESULTS: All original observations by Willert and Henkel (Z Orthop Ihre Grenzgeb. 107:663-75, 1970), were verified. Radial rays of the hand disappeared early, but the foot was spared until late. Radiology confirms that bone reduction in the hand (aplasia or hypoplasia in the thumb and index finger) coincides with sensory segmental nerve C6. In the foot, reduction of the toes is rare, but mesenchymal excess (polydactyly) occurs in the hallux (L5 sclerotome), usually associated with absent tibia (L4 sclerotome). Histology confirms skeletal mesenchymal components to be unremarkable, contrasting with grossly abnormal bony architecture, a striking discordance between microscopic and macroscopic findings. No necrosis or vascular pathology was seen. CONCLUSION: The basic lesion was an abnormal quantity rather than quality of mesenchyme. Cell populations result from cellular proliferation, controlled in early limb bud formation by neurotrophism. Thalidomide is a known sensory neurotoxin in adults. In the embryo, sensorineural injury alters neurotrophism, causing increased or diminished cell proliferation in undifferentiated mesenchyme. Differentiation into normal cartilage occurs later, but within an altered mesenchymal mass. Reduction or excess deformity results, with normal histology, a significant finding. The primary pathological condition is not in the skeleton, but in the nerves.


Assuntos
Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Extremidades/diagnóstico por imagem , Deformidades Congênitas dos Membros/induzido quimicamente , Deformidades Congênitas dos Membros/diagnóstico por imagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Talidomida/efeitos adversos , Anormalidades Induzidas por Medicamentos/embriologia , Anormalidades Induzidas por Medicamentos/etiologia , Extremidades/embriologia , Extremidades/inervação , Humanos , Recém-Nascido
18.
Drug Saf ; 42(3): 389-400, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30284214

RESUMO

INTRODUCTION: Adverse effects of medications taken during pregnancy are traditionally studied through post-marketing pregnancy registries, which have limitations. Social media data may be an alternative data source for pregnancy surveillance studies. OBJECTIVE: The objective of this study was to assess the feasibility of using social media data as an alternative source for pregnancy surveillance for regulatory decision making. METHODS: We created an automated method to identify Twitter accounts of pregnant women. We identified 196 pregnant women with a mention of a birth defect in relation to their baby and 196 without a mention of a birth defect in relation to their baby. We extracted information on pregnancy and maternal demographics, medication intake and timing, and birth defects. RESULTS: Although often incomplete, we extracted data for the majority of the pregnancies. Among women that reported birth defects, 35% reported taking one or more medications during pregnancy compared with 17% of controls. After accounting for age, race, and place of residence, a higher medication intake was observed in women who reported birth defects. The rate of birth defects in the pregnancy cohort was lower (0.44%) compared with the rate in the general population (3%). CONCLUSIONS: Twitter data capture information on medication intake and birth defects; however, the information obtained cannot replace pregnancy registries at this time. Development of improved methods to automatically extract and annotate social media data may increase their value to support regulatory decision making regarding pregnancy outcomes in women using medications during their pregnancies.


Assuntos
Anormalidades Induzidas por Medicamentos , Sistemas de Notificação de Reações Adversas a Medicamentos/organização & administração , Farmacoepidemiologia/métodos , Mídias Sociais , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Gravidez , Sistema de Registros
19.
Eur J Obstet Gynecol Reprod Biol ; 232: 18-21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30453167

RESUMO

OBJECTIVE: To evaluate the effects of ionizing radiation exposure during the first trimester of pregnancy in usual clinical situations. STUDY DESIGN: We conducted a prospective observational cohort study using data collected between 1987 and 2014. This database was authorized by the French "Commission Nationale de l'Informatique et des Libertés". The exposed group consisted of 319 pregnant women exposed to sub diaphragmatic ionizing radiations for diagnostic purposes, during the first trimester of pregnancy, and the control group consisted of 319 pregnant women without any exposure or exposed to non-teratogenic agents. Data on maternal history and radiations exposure were collected on first contact, and pregnancy outcomes were documented at follow-up. An univariate analysis was performed to compare both groups for the main outcomes. RESULTS: Exposure to sub diaphragmatic ionizing radiation for diagnosis purpose (median fetal dose of 3.1 mGy [0.2-130.0]) during the first trimester of pregnancy was not significantly associated with an increased risk of malformations (1.5% vs 1.8%, p = 1.00), miscarriage (7.8% vs 7.2%, p = 0.88), in utero fetal death (0.3% vs 0%, p = 1.00) or fetal growth restriction (5.4% vs 3.5%, p = 0.62). CONCLUSION: Pregnant women exposed to irradiant diagnostic procedures do not present a higher risk of malformations, miscarriage, in utero fetal death or fetal growth restriction and should be reassured, even if the examination focused on the pelvis.


Assuntos
Aborto Espontâneo/etiologia , Retardo do Crescimento Fetal/etiologia , Exposição Materna/efeitos adversos , Primeiro Trimestre da Gravidez/efeitos da radiação , Efeitos Tardios da Exposição Pré-Natal/etiologia , Radiação Ionizante , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Feminino , Humanos , Gravidez , Resultado da Gravidez , Estudos Prospectivos
20.
Diagn Microbiol Infect Dis ; 93(3): 238-242, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30442509

RESUMO

Tetracycline antimicrobials entered into clinical usage in the late 1940s. Permanent dental staining from tetracyclines was first appreciated in 1956, eventually leading to avoidance of this class of antibiotics whenever possible in young children and pregnant or breastfeeding women. Doxycycline, introduced in 1967, binds calcium less avidly than prior tetracyclines and is regarded by some authorities as safe to prescribe for pregnant women and young children. Review of the available data, however, suggests that this interpretation may be incorrect or at least premature. In conclusion, until more definitive data are developed, doxycycline should continue to be only selectively prescribed for young children and pregnant or breastfeeding women for whom alternative, safer antibiotics are not available, and courses of treatment should be of as short a duration as possible.


Assuntos
Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Anormalidades Induzidas por Medicamentos/etiologia , Antibacterianos/efeitos adversos , Aleitamento Materno , Doxiciclina/efeitos adversos , Feminino , Humanos , Gravidez , Segurança , Descoloração de Dente/etiologia
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