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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.
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
4.
Neurology ; 93(9): e831-e840, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31391249

RESUMO

OBJECTIVE: Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP). METHODS: EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000-2005 (n = 4,760), 2006-2009 (n = 3,599), and 2010-2013 (n = 2,949). RESULTS: There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000-2005 to 4.4% in 2010-2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy. CONCLUSIONS: There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Feminino , Humanos , Internacionalidade , Pessoa de Meia-Idade , Padrões de Prática Médica/tendências , Gravidez , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
BJOG ; 126(9): 1127-1133, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31006176

RESUMO

BACKGROUND: At the end of the 1980s, several studies suggested a potential increased risk of neural tube defects (NTDs) with ovulation induction/fertility drugs, especially with clomiphene citrate (CC). A previous meta-analysis of observational studies evaluating the risk of NTDs associated with the use of CC performed in 1995 found a risk ratio of 1.08 (95% CI 0.76-1.51). Since then, additional studies have been published and the risk of NTDs associated with periconceptional CC exposure may have changed. OBJECTIVE: To perform an updated quantitative meta-analysis of the risk of NTDs associated with periconceptional CC exposure. SEARCH STRATEGY: MEDLINE, Web of Science, and Scopus were searched (October 2018). SELECTION CRITERIA: Comparative cohort and case-control studies investigating the risk of NTDs after periconceptional CC exposure. DATA COLLECTION AND ANALYSIS: Pooled effect sizes with corresponding 95% CIs were calculated using random effects models, comparing the risk of NTDs between pregnancies exposed and not exposed to CC. MAIN RESULTS: Thirteen studies met the inclusion criteria, totalling 218 819 pregnancies. Periconceptional exposure to CC was not significantly associated with an increased risk of NTDs (pooled odds ratio 1.21, 95% CI 0.88-1.66). No heterogeneity between studies was observed (I2  = 26%). A funnel plot and asymmetry test were not suggestive of publication bias. CONCLUSION: Our meta-analysis confirms that exposure to CC before or in early pregnancy was associated with a 21% increased risk of NTD in relation to CC exposure; however, this increased risk is not statistically significant. TWEETABLE ABSTRACT: A new meta-analysis finds that clomiphene citrate exposure before or in early pregnancy is not associated with an increased risk of NTDs.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Clomifeno/efeitos adversos , Fármacos para a Fertilidade Feminina/efeitos adversos , Exposição Materna/efeitos adversos , Defeitos do Tubo Neural/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/tratamento farmacológico , Defeitos do Tubo Neural/induzido quimicamente , Estudos Observacionais como Assunto , Razão de Chances , Indução da Ovulação/métodos , Gravidez , Fatores de Risco
6.
Clin Exp Rheumatol ; 37(6): 976-982, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943142

RESUMO

OBJECTIVES: To determine the association between perinatal biologic use and congenital anomalies in women with autoimmune disease. METHODS: We linked population-based administrative health data including information on all medications with a perinatal registry in British Columbia, Canada. Women with one or more autoimmune diseases who had pregnancies between January 1st, 2002 and December 31st, 2012 were included. Exposure to biologics was defined as having at least one biologic prescription 3 months before conception or during the first trimester of pregnancy. Each exposed pregnancy was matched with five unexposed pregnancies using high dimensional propensity scores (HDPS). Logistic regression modelling was used to evaluate the association between biologics use and congenital anomalies. RESULTS: The HDPS-matched cohort included 117 pregnancies (107 women) exposed to biologics, and 585 pregnancies (562 women) that were not exposed to biologics during the period of interest; 6% of newborns had ≥1 congenital anomalies at birth, in the exposed and unexposed groups. There were no obvious patterns with regards to the congenital anomalies observed in the biologics exposed group. In primary analysis, the OR for the association between biologic exposure and congenital anomalies was 1.06 (95%CI 0.46-2.47). Secondary and sensitivity analyses did not change the results appreciably. CONCLUSIONS: These population-based data suggest that the use of biologics before and during pregnancy is not associated with an increased risk of congenital anomalies.


Assuntos
Doenças Autoimunes , Produtos Biológicos , Anormalidades Congênitas/epidemiologia , Gestantes , Anormalidades Induzidas por Medicamentos/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Canadá , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez
7.
BMC Womens Health ; 19(1): 51, 2019 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-30943953

RESUMO

BACKGROUND: Between 1957 and 1961 the substance Thalidomide was sold in West Germany and taken by many women as a sedative during pregnancy. This lead to miscarriages and infants been born with several severe malformations. The aim of this study was to describe the current situation of women impaired by Thalidomide induced embryopahty in North Rhine-Westphalia (Nordrhein-Westfalen), Germany, in comparison with the results found in a study done in 2002 by Nippert et al. METHODS: Questionnaires as well as examinations were performed. Data were compared using descriptive and inductive statistical methods. RESULTS: Both studies show that women impaired by Thalidomide embryopathy face a poorer health status than women their age in the general population and live in fear of further deteriorating health. The majority can only work reduced hours or are already retired due to poor health. Most of those who need assistance are being assisted by their social environment, while professional care is still utilized in only few cases. CONCLUSIONS: An obvious need for a shift in the provision of assistance and/or care provided was found as the social environment supporting the impaired women is also aging and therefore in high danger of breaking apart. TRIAL REGISTRATION: The study has been registered at German Clinical Trials Register, DRKS00010593 , on 07.06.2016 retrospectively.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Imunossupressores/efeitos adversos , Talidomida/efeitos adversos , Saúde da Mulher/estatística & dados numéricos , Adulto , Estudos Transversais , Feminino , Doenças Fetais/epidemiologia , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
8.
J Acquir Immune Defic Syndr ; 81(4): 371-378, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939532

RESUMO

BACKGROUND: Birth outcome data with dolutegravir exposure during pregnancy, particularly in the first trimester, are needed. SETTING: Data were prospectively collected from the Antiretroviral Pregnancy Registry and European Pregnancy and Paediatric HIV Cohort Collaboration. METHODS: We reviewed 2 large, independent antiretroviral pregnancy registries to assess birth outcomes associated with maternal dolutegravir treatment during pregnancy. RESULTS: Of 265 pregnancies reported to the Antiretroviral Pregnancy Registry, initial exposure to dolutegravir occurred at conception or first trimester in 173 pregnancies and during the second or third trimester in 92 pregnancies. There were 246 (92.8%) live births resulting in 255 neonates (9 twins), 6 (2.3%) induced abortions, 11 (4.2%) spontaneous abortions, and 2 (0.8%) stillbirths. Birth defects occurred in 7 (2.7%) of 255 live-born neonates, 5 (3.1%) of 162 (includes 6 twins) with conception/first-trimester exposure. Of 101 pregnancies reported to the European Pregnancy and Paediatric HIV Cohort Collaboration, outcomes were available for 84 pregnancies (16 continuing to term and 1 lost to follow-up). There were 81 live births (80 with known initial dolutegravir exposure at conception or first, second, and third trimesters in 42, 21, and 17 live births, respectively), 1 stillbirth (second-trimester exposure), 1 induced abortion (first-trimester exposure), and 1 spontaneous abortion (first-trimester exposure), respectively. Birth defects occurred in 4 live births (4.9%; 95% confidence interval: 1.4 to 12.2), 3 of 42 (7.1%) with exposure at conception or first trimester. CONCLUSIONS: Our findings are reassuring regarding dolutegravir treatment of HIV infection during pregnancy but remain inconclusive because of small sample sizes.


Assuntos
Anormalidades Induzidas por Medicamentos/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/epidemiologia , Aborto Induzido/estatística & dados numéricos , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Fertilização , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Sistema de Registros , Natimorto , Estados Unidos , Adulto Jovem
9.
Pharmacol Res Perspect ; 7(1): e00452, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30766684

RESUMO

Birth defects are important causes of neonatal morbidity and mortality. A good understanding of the etiology is a vital step toward developing improved treatment and preventive strategies. We conducted an audit of medical records of newborns with birth abnormalities in a tertiary hospital over a 10-year period, using a Pro forma designed to collect information on obstetric history, antenatal history, sociodemographics of parents, and the type of birth abnormality. Of the 180 medical records reviewed, female babies were 92 (51.1%) and male babies were 86 (47.8%). The mean age of the fathers was 38.2 + 6.2, and mothers 31.8 + 4.9. Majority 115 (63.9%) of the mothers had records of acute illnesses, and 23 (12.8%) chronic illnesses during pregnancy. Unspecified febrile illness 44 (38.3%), malaria 40 (34.8%), typhoid 8 (6.9%), hypertension 13 (56.5%), pregestational diabetes 4 (17.4%), and HIV 3 (13.0%) were the commonest maternal pathologies. Most of the documented birth abnormalities were Down's syndrome 34 (15.2%); congenital hydrocephalus 32 (14.3%); acyanotic congenital heart defect 30 (13.4%); deformity of the digits 26 (11.6%); and ventricular septal defect 20 (8.9%). The prevalence of maternal pathologies calls for concern, as these may be implicated in birth defects, therefore should be further investigated in future studies.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Congênitas/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Anormalidades Congênitas/etiologia , Feminino , Humanos , Recém-Nascido , Masculino , Idade Materna , Pessoa de Meia-Idade , Nigéria , Gravidez , Complicações na Gravidez/fisiopatologia , Prevalência , Estudos Retrospectivos , Teratogênese , Teratogênios/toxicidade , Centros de Atenção Terciária , Adulto Jovem
10.
Reprod Toxicol ; 85: 65-74, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30738954

RESUMO

OBJECTIVE: To investigate whether maternal exposure to quinolones, fluoroquinolones and specifically ciprofloxacin is associated with major malformations and other adverse pregnancy outcomes. METHODS: MEDLINE/PubMed, Embase and Reprotox® databases were searched. Observational studies with an exposed and control group were included. RESULTS: Analysis of 8 cohort and 2 case-control studies showed no significant increases in rates of major malformations for quinolone (OR, 1.04; 95% CI 0.89-1.21), fluoroquinolone (RR, 0.89; 95% CI 0.70-1.14) and ciprofloxacin exposure (RR, 0.72; 95% CI 0.43-1.19). For fluoroquinolones, live birth rate was significantly decreased (RD, -0.04; 95% CI -0.08 to -0.01) whereas elective termination rate (RD, 0.04; 95% CI 0.02-0.05) was significantly increased. CONCLUSIONS: Quinolone, fluoroquinolone and ciprofloxacin exposure were not associated with a significant increase in major malformations and adverse pregnancy outcomes, other than significantly decreased live birth rate and increased elective termination rate which may be the indicators of misperceived teratogenic risk.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antibacterianos/toxicidade , Exposição Materna , Resultado da Gravidez/epidemiologia , Quinolonas/toxicidade , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez
11.
Acta Ophthalmol ; 97(5): 505-509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30479070

RESUMO

PURPOSE: To investigate whether exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy was associated with an increased risk of malformations in humans. METHODS: All women giving live birth between 1997 and 2011 in Denmark were included in this nationwide cohort study. All women redeeming at least one prescription of antazoline-naphazoline eye drops during the first 84 days of pregnancy were identified. Logistic regression was used to estimate the odds ratios of malformations among exposed offspring compared to non-exposed offspring. RESULTS: We identified 977 706 births between 1997 and 2011. A total of 3061 women (0.32%) were exposed to antazoline-naphazoline eye drops in the first trimester of pregnancy. The rate of congenital malformations was 3.0% (n = 93) in exposed offspring and 3.5% (n = 33 594) in unexposed offspring. First-trimester exposure to antazoline-naphazoline was not associated with major congenital malformations overall (odds ratio: 0.88, 95% confidence interval: 0.71-1.09) or with any specific major malformation. The number of redeemed prescriptions was unchanged during all trimesters of pregnancy as compared to before and after pregnancy (p < 0.05). CONCLUSION: Exposure to antazoline-naphazoline eye drops in the first trimester of pregnancy appears not to be associated with increased teratogenic risk.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antazolina/efeitos adversos , Nafazolina/efeitos adversos , Vigilância da População/métodos , Sistema de Registros , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Antazolina/administração & dosagem , Antialérgicos/administração & dosagem , Antialérgicos/efeitos adversos , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Recém-Nascido , Masculino , Nafazolina/administração & dosagem , Descongestionantes Nasais/administração & dosagem , Descongestionantes Nasais/efeitos adversos , Soluções Oftálmicas , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Acta Neurol Scand ; 139(1): 42-48, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30109700

RESUMO

OBJECTIVES: To gain insight into the main advantages and disadvantages that might result from valproate being unavailable for women who intend to become pregnant. MATERIALS AND METHODS: Analysis of data from the Australian Pregnancy Register concerning pregnancies exposed to valproate (N = 501) and pregnancies where previous valproate intake had been ceased before pregnancy (N = 101). RESULTS: The risk of foetal malformation associated with valproate exposure during pregnancy was dose-related, and there was a tendency for the more major malformations, including those often managed by therapeutic abortion, for example spina bifida, to occur at higher valproate doses. Had there been no exposure to valproate during pregnancy, some 80% of the foetal malformations that occurred might have been avoided. Cessation of previous valproate therapy before pregnancy was associated with an increased hazard of seizure-affected pregnancy. This was particularly the case for women with generalized epilepsies, in whom the incidence of seizure-affected pregnancy was increased by 50% to nearly 100%. CONCLUSIONS: Avoiding valproate intake during pregnancy is likely to reduce the incidence of foetal malformation, but at a cost of worsened maternal epilepsy control. Individualization of treatment is particularly important in considering withdrawal of valproate in the light of the fact that it is much more widely used in generalized epilepsy, there being fewer alternative drugs than for focal epilepsy and withdrawal is not without risk for both mother and baby. This study may provide a quantitative basis for assessing the balance between benefit and disadvantage for individual women with valproate-treated epilepsy who are considering pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversos , Adulto , Austrália/epidemiologia , Feminino , Humanos , Gravidez , Sistema de Registros , Risco , Convulsões/tratamento farmacológico
13.
Environ Sci Pollut Res Int ; 26(1): 91-100, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30411285

RESUMO

The need to maximize agricultural productivity has made pesticides an indispensable part of current times. Farmers are unaware of the lurking consequences of the pesticide exposure, which endanger their health. It also puts the unsuspecting consumers in peril. The pesticides (from organophosphates, organochlorine, and carbamate class) disrupt the immune and hormonal signaling, causing recurrent inflammation, which leads to a wide array pathologies, including teratogenicity. Numerous farmers have fallen victim to neural disorders-driven suicides and lungs, prostate/breast cancer-caused untimely deaths. Green revolution which significantly escalated agricultural productivity is backfiring now. It is high time that environmental and agricultural authorities act to restrain the excessive usage of the detrimental chemicals and educate farmers regarding the crisis. This review discusses the biological mechanisms of pesticide-driven pathogenesis (such as the activation or inhibition of caspase, serine protease, acetylcholinesterase) and presents the pesticide-exposure-caused health deterioration in USA, India, and Africa. This holistic and critical review should be an eye-opener for general public, and a guide for researchers.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Neoplasias/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Transtornos Psicóticos/etiologia , Anormalidades Induzidas por Medicamentos/epidemiologia , África , Fazendeiros , Feminino , Humanos , Índia , Masculino , Neoplasias/epidemiologia , Praguicidas/análise , Transtornos Psicóticos/epidemiologia , Suicídio/tendências , Estados Unidos
14.
J Acquir Immune Defic Syndr ; 80(3): 264-268, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531300

RESUMO

BACKGROUND: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland. METHODS: The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure. RESULTS: A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion. CONCLUSIONS: The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Quinolonas/efeitos adversos , Raltegravir Potássico/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Irlanda/epidemiologia , Gravidez , Quinolonas/uso terapêutico , Raltegravir Potássico/uso terapêutico , Natimorto , Reino Unido/epidemiologia
15.
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
16.
Seizure ; 65: 6-11, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30593875

RESUMO

PURPOSE: This paper reports additional data supplementing earlier publications based on Australian Pregnancy Register (APR) data. METHOD: Over 20 years, the APR has collected Information on pregnancies in Australian women with epilepsy (WWE), untreated WWE and those taking AEDs for other indications. Contact is by telephone, at set intervals. Treatment is not interfered with. Data are analysed using conventional statistical techniques, confidence interval methods, and logistic regression. RESULTS: By 2018, the APR contained details of 2148 pregnancies. AEDs were taken throughout 1972 of the pregnancies (91.8%). The remaining 176 (8.2%) did not receive AEDs, at least early in pregnancy. There were (i) dose-related increased incidences of pregnancies carrying foetal malformations associated with maternal intake of valproate and topiramate when topiramate was a component of AED polytherapy (P < .05), (ii) a similar dose-related trend in relation to carbamazepine intake, (iii) no evidence that levetiracetam and lamotrigine were unsafe from the foetal standpoint, (iv) insufficient data to permit conclusions regarding teratogenicity in relation to other AEDs, and (v) no evidence that pre-conception folate supplementation reduced the hazard of AED-associated foetal malformation. AED polytherapy did not increase foetal hazard unless valproate or topiramate was involved in the AED combination. Genetic factors probably contributed to the malformation hazard. Seizures occurring in earlier pregnancy probably did not contribute to the malformation hazard. CONCLUSIONS: If it were not for the importance of maintaining seizure control, the above findings suggest that it would be better to avoid using certain AEDs, particularly valproate and topiramate, during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Doenças Fetais/induzido quimicamente , Complicações na Gravidez/induzido quimicamente , Sistema de Registros , Anormalidades Induzidas por Medicamentos/epidemiologia , Adulto , Austrália/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Doenças Fetais/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Fatores de Tempo , Adulto Jovem
17.
Psiquiatr. biol. (Internet) ; 25(3): 103-107, sept.-dic. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-175115

RESUMO

El uso de medicación en el embarazo es siempre un asunto problemático, dada la ausencia de datos suficientes sobre los que asentar las decisiones clínicas y la incertidumbre asociada. Salvo en casos claros de teratogenicidad (en el caso de los psicofármacos, por ejemplo, el ácido valproico) el uso de medicación en el embarazo es siempre una cuestión de sentido común, y sobre todo, de una cuidadosa evaluación riesgo-beneficio. En las enfermedades mentales los riesgos para la madre y el feto derivados de la ausencia de tratamiento pueden superar con creces los que se derivan de la exposición a la medicación, especialmente en el caso de trastornos mentales graves como la esquizofrenia, el trastorno bipolar o la depresión grave. En el caso de la medicación antipsicótica, el conocimiento disponible acerca de sus efectos sobre el desarrollo fetal, el periodo neonatal y el desarrollo neurológico y conductual a largo plazo es limitado, por lo que resulta difícil establecer un criterio general para su uso, máxime si se tiene en cuenta que las conclusiones y las recomendaciones derivadas de los estudios disponibles no siempre son coincidentes. Esto obliga al clínico a sopesar las ventajas e inconvenientes de estos fármacos en condiciones de incertidumbre, incluyendo los riesgos que conllevaría la interrupción del tratamiento, y de hacerlo en un contexto de información clara y decisiones compartidas para la paciente


The use of medication in pregnancy is always a problematic issue, given the lack of sufficient data on which to base clinical decisions, as well as the associated uncertainty. Except in clear cases of teratogenicity, such as thalidomide, or in the case of psychotropic drugs —valproic acid—, the use of medication in pregnancy is always a matter of common sense, and above all, of a careful risk-benefit evaluation. In mental illness, the risks to the mother and the foetus in the absence of treatment can far exceed those arising from exposure to medication, especially in the case of serious mental disorders such as schizophrenia, bipolar disorder, or severe depression. In the case of antipsychotic medication, the available knowledge about its effects on foetal development, the neonatal period, and long-term neurological and behavioural development is limited. This makes it difficult to establish a general criterion for its use, especially if it is taken into account that the conclusions and recommendations derived from the available studies are not always coincident. This forces the clinician to weigh the advantages and disadvantages of these drugs under conditions of uncertainty, including the risks that the interruption of treatment would entail, and to do so in a context of clear information and shared decisions for the patient


Assuntos
Humanos , Feminino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Anormalidades Induzidas por Medicamentos/epidemiologia , Teratogênese , Exposição Materna/efeitos adversos
18.
BMC Med ; 16(1): 205, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30415641

RESUMO

BACKGROUND: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication. METHODS: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs). RESULTS: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32). CONCLUSIONS: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Inibidores de Captação de Serotonina/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Gravidez , Primeiro Trimestre da Gravidez , Risco
19.
Pharmacoepidemiol Drug Saf ; 27(12): 1302-1308, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30379378

RESUMO

PURPOSE: There is little data on the effects of cancer chemotherapy in pregnant women. The objective of this study was to describe pregnancy outcomes of women exposed to cancer chemotherapy, recorded in the French Terappel database. METHODS: We performed a descriptive, prospective study of the pregnancies of women exposed to cancer chemotherapy recorded in Terappel between June 1984 and December 2016. Terappel is a French database that has recorded questions of health professionals and/or individuals at the Regional Pharmacovigilance Centres about drugs and pregnancy. For each question, pregnancies are monitored and the outcome is recorded in the database. RESULTS: In total, 75 questions about "anti-cancer drugs and pregnancy" received by 16 Regional Pharmacovigilance Centres between 1997 and 2016 were recorded in Terappel. Breast cancer accounted for 62.7% of the cases, followed by leukaemia (13.3%) and lymphoma (9.3%). Cyclophosphamide is the leading anti-cancer drug with 40.0% of exposed pregnant women, followed by 5-fluorouracil (34.7%), epirubicin (32.0%), tamoxifen (26.7%), and doxorubicin (16.0%). Among the 75 pregnancies, we observed 55 births with 57 children (73.3%) (two cases of twins), nine medical terminations of pregnancy (12.0%), six voluntary terminations of pregnancy (8.0%), three intrauterine foetal deaths (4.0%), and two miscarriages (2.7%). We found a malformation rate of 7.8%. Sixteen of 57 (28.1%) newborns developed one or more neonatal pathologies. CONCLUSION: Pregnancy of women taking anti-cancer drugs resulted in birth in 73% of cases. Nevertheless, pregnant women exposed to cancer chemotherapy remains at risk of malformations and neonatal conditions related to prematurity and drugs.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Farmacovigilância , Gravidez , Estudos Prospectivos , Adulto Jovem
20.
Pharmacoepidemiol Drug Saf ; 27(12): 1309-1315, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30240072

RESUMO

PURPOSE: The recent expansion of electronic health and medical record systems may present an opportunity to generate robust post-approval safety data and obviate the limitations of prospective pregnancy exposure registries. We examined and compared, over the same time frame, the outcomes of triptan exposure in pregnancy using (1) a retrospective claims database and (2) a previously completed pregnancy registry. METHODS: Using the Marketscan database, the risk of major birth defects was ascertained in live-born infants whose birth mothers were exposed to sumatriptan, naratriptan, or sumatriptan/naproxen during pregnancy. The frequencies of outcomes observed were compared with the findings of the 16-year sumatriptan, naratripan, and sumatriptan/naproxen prospective pregnancy registry. RESULTS: About 5120 pregnancies were identified in the retrospective claims cohort in contrast to 617 included in the prospective registry during the same time frame. The proportion of major birth defects among first-semester sumatriptan exposures was 4.0%, which is exactly the same as the proportion of major birth defects reported for first-semester sumatriptan exposures in the registry. There were very few non-livebirth outcomes in both the claims analyses and registry. CONCLUSIONS: These results confirm broad agreement between the database analysis and the registry regarding the safety of triptans during pregnancy. Of note, the number of triptan-exposed pregnancies identified in this large US database was about 7-fold that included in the prospective registry over the same time frame. The findings of this study support an approach of using existing health care database (s) in the post-approval assessment of medication exposure in pregnancy.


Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Transtornos de Enxaqueca/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Triptaminas/efeitos adversos , Anormalidades Induzidas por Medicamentos/etiologia , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Combinação de Medicamentos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Recém-Nascido , Naproxeno , Piperidinas , Gravidez , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Sumatriptana , Estados Unidos/epidemiologia , Adulto Jovem
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