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In 2018, a significant neural tube defects (NTD) signal was reported after pre-conceptional exposure to dolutegravir, but was not confirmed in further analysis. Since 2019, dolutegravir-based regimen, an integrase inhibitor (INI), is recommended by WHO as the most-effective first-line therapy in all patients living with HIV. To explore the potential INI-related teratogenic effect, we searched disproportionate signals between exposure to INI-class drugs and congenital anomalies, compared to non-INI drugs, using the international pharmacovigilance database, VigiBase®. We selected all the reports registered in VigiBase® between 01/01/2007 and 30/03/2021 on any antiretroviral drug-related fetal or neonatal adverse drug reactions, declared either in children (<2 years) exposed in utero or in pregnant women (12-50 years). A case/non-case study was conducted to detected signals between congenital anomalies and prenatal exposure to any INI-class drug, compared to non-INI drugs, by estimating adjusted reporting odds ratios (aROR) with 95% confidence intervals (95%CI). We identified 2521 unique reports, among which 664 (26.3%) were related to INI-class use. Overall, 520 congenital anomalies were cited from 327 unique reports, of whom 31.0% were INI-related. Compared to non-INI drugs, no significant disproportionate reporting signal between prenatal exposure to INI-class drugs and congenital anomalies was found (aROR 1.13; 95% CI:0.85-1.51). However, specific significant signals were reported for raltegravir/elvitegravir/dolutegravir drug exposure and urinary malformations (aROR 2.43; 95%CI:1.08-5.43), digestive malformations (aROR 3.09; 95%CI:1.22-7.84), and NTDs (aROR 3.02; 95%CI:1.09-8.37). Although specific congenital anomalies signals associated with raltegravir/elvitegravir/dolutegravir exposure were notified, causal relationship needs to be further investigated in prospective studies.
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Anomalías Inducidas por Medicamentos , Bases de Datos Factuales , Compuestos Heterocíclicos con 3 Anillos , Farmacovigilancia , Piridonas , Humanos , Embarazo , Femenino , Adulto , Adolescente , Anomalías Inducidas por Medicamentos/epidemiología , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Piridonas/efectos adversos , Adulto Joven , Recién Nacido , Niño , Piperazinas/efectos adversos , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de Integrasa VIH/uso terapéutico , Oxazinas/efectos adversos , Raltegravir Potásico/efectos adversos , Raltegravir Potásico/uso terapéutico , Preescolar , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , QuinolonasRESUMEN
INTRODUCTION: Respiratory tract disorders are common in children. However, there is no available data on the prescription of respiratory medications for children in France. This study aimed to provide an overview of medications for obstructive airway diseases prescriptions for children during the initial ten years of their lives within POMME, a French population-based cohort of children. MATERIAL AND METHODS: This longitudinal, population-based study used data from the French POMME birth cohort, comprising children born in Haute Garonne between July 2010 and June 2011. Anonymous medical information, including medication reimbursement data, was collected between ages 0 and 10 years. Exposure was defined as at least one prescription for respiratory medications (ATC code R03*), focusing on specific subclasses. Data were analyzed by age, season, and prescribing physicians' specialties. RESULTS: Out of 5956 children, 4951 (83.1 %) received respiratory medication prescriptions. Inhaled corticosteroids (ICSs) were the most prescribed (95.3 %), followed by short-acting ß2-agonists (68.8 %). The number of prescriptions increased with age, except for ICSs alone, which peaked between 6 months and 2 years. The average number of prescriptions per child was relatively low. DISCUSSION: This study highlighted high prescription rates of respiratory medications in children under 10 years, with ICSs being the most prevalent. While these medications are primarily intended for asthma management, the findings suggested a significant proportion of off-label prescriptions, especially in young children. Further research and clinical guidance are warranted to ensure appropriate medication use in the pediatric population.
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Corticoesteroides , Humanos , Lactante , Preescolar , Estudios Longitudinales , Niño , Francia , Masculino , Femenino , Recién Nacido , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Administración por Inhalación , Prescripciones de Medicamentos/estadística & datos numéricos , Bases de Datos Factuales , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Fármacos del Sistema Respiratorio/uso terapéuticoRESUMEN
The objective of this cohort study was to describe the French population of pregnant women vaccinated against coronavirus disease 2019 (COVID-19), their pregnancy outcomes and the health status of their newborns (malformation rate, neonatal diseases, etc.), and to proactively collect and analyze reported adverse reactions over time. We conducted a prospective study using an online questionnaire. Women vaccinated during pregnancy who wanted to participate were asked to complete an inclusion questionnaire (dates of pregnancy and vaccination COVID-19, etc.), a questionnaire on the potential occurrence of adverse reactions (time of onset, type of adverse reaction, etc.) of the vaccination, sent 1 month after the injection, and a final questionnaire on the outcome of the pregnancy and the health status of the child. A total of 938 women were prospectively included in this first French study. A total of 132 women reported having had at least 1 adverse reaction following vaccination during pregnancy (14.1%), including few 'serious' adverse reaction (5.3%). There were no signals of adverse reactions during continuous monitoring. Among the 938 pregnant women, 22.4% received the vaccination COVID-19 during the first trimester, 64.2% during the second and 33.4% during the third trimester (some women have had several injections in different trimesters). Among the 938 women, 4.3% developed gestational hypertension and 13.9% diabetes; 3.3% had intrauterine growth restriction and 7.8% threatened preterm delivery. These rates are comparable to those observed in the French general population. Among live births, the rate of preterm birth was 5.1%. We reported a prevalence of major malformations of 3.9%, which is comparable to that reported by European Surveillance of Congenital Anomalies (EUROCAT), with a rate of 3.5% of major malformations in the general population of mainland France. In conclusion, our study did not demonstrate any particular safety signals in the event of vaccination with a Covid-19 vaccine during pregnancy.
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INTRODUCTION: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.
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Deformidades Congénitas de las Extremidades Superiores , Humanos , Francia/epidemiología , Femenino , Masculino , Análisis por Conglomerados , Factores de Riesgo , Extremidad Superior , Análisis Espacio-Temporal , Niño , Exposición a Riesgos Ambientales/efectos adversos , LactanteRESUMEN
For several years, fertility disorders have been on the increase worldwide. These disorders affect both sexes, but are more pronounced in men; and in half of cases the etiology is unknown. The role of drugs in male infertility has been little studied to date. Most of the available data comes from experimental animal studies, with all their limitations. With the exception of a few drugs, such as certain anticancer agents, human data are rare. This article describes the mainly drugs known to have deleterious effects on male fertility, the mechanisms leading to these effects and methods used to assess the risk of drug-induced male infertility. It underlines the need for further work in experimental research, clinical trials and post-marketing surveillance to improve our knowledge of drugs that induce male infertility. Although these adverse effects are not life-threatening, they can have a significant impact on patients' lives.
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Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infertilidad Masculina , Femenino , Animales , Humanos , Masculino , Fertilidad , Infertilidad Masculina/inducido químicamente , Infertilidad Masculina/epidemiología , Infertilidad Masculina/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Factores de Riesgo , Antineoplásicos/efectos adversosRESUMEN
OBJECTIVE: In recent years, safety concerns about modafinil exposure during pregnancy have emerged. In particular, increased risks for major congenital anomalies (MCA) and impaired fetal growth were reported, although study results were conflicting. Our investigation aims to examine previously reported safety signals. METHOD: Multicenter case series based on data from 18 Teratology Information Services from 12 countries. Modafinil exposed pregnancies with an estimated date of birth before August 2019 were included in this study. For prospectively ascertained pregnancies, cumulative incidences of pregnancy outcomes, rate of nonchromosomal MCA in first trimester exposed pregnancies and percentiles of neonatal/infant weight and head circumference (HC) were calculated. Potential dose-dependent effects on fetal growth were explored by linear regression models. Retrospectively ascertained cases were screened for pattern of MCA and other adverse events. RESULTS: One hundred and seventy-five prospectively ascertained cases were included, of which 173 were exposed at least during the first trimester. Cumulative incidences for live birth, spontaneous abortion and elective termination of pregnancy were 76.9% (95% CI, 68.0%-84.8%), 9.3% (95% CI, 5.0%-16.9%), and 13.9% (95% CI, 8.1%-23.1%), respectively. Nonchromosomal MCA was present in 3/150 live births, corresponding to an MCA rate of 2.0% (95%CI, 0.6%-6.1%), none were reported in pregnancy losses. Compared to reference standards, birth weight (BW) tended to be lower and neonatal HC to be smaller in exposed newborns (data available for 144 and 73 of 153 live births, respectively). In nonadjusted linear regression models, each 100 mg increase of average dosage per pregnancy day was associated with a decrease in standard deviation score (SDS) of -0.28 SDS (95% CI, -0.45 to -0.10) for BW and of -0.28 SDS (95% CI, -0.56 to 0.01) for HC. Screening of 22 retrospectively reported cases did not reveal any specific pattern of MCA or other adverse outcomes. CONCLUSION: The results do not indicate an increased risk of MCA after in utero exposure to modafinil, but a tendency toward lower BW and reduced neonatal HC. However, these findings should be regarded as preliminary. Until further studies allow for a definite conclusion, modafinil should not be used during pregnancy.
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Background: Among antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs) are particularly expected to increase the risk of hypertensive disorders of pregnancy (HDP) with regard to their biological mechanism. We aimed to evaluate the association between prenatal exposure to SNRI and HDP.Methods: In EFEMERIS, a French database including pregnant women covered by the French Health Insurance System of Haute-Garonne (2004-2019), we compared the incidence of HDP among women exposed to SNRI monotherapy during the first trimester of pregnancy to the incidence among 2 control groups: (1) women exposed to selective serotonin reuptake inhibitor (SSRI) monotherapy during the first trimester and (2) women not exposed to antidepressants during pregnancy. We conducted crude and also multivariate logistic regressions.Results: Of the 156,133 pregnancies, 143,391 were included in the study population, including 210 (0.1%) in the SNRI group, 1,316 (0.9%) in the SSRI group, and 141,865 (98.9%) in the unexposed group. After adjustment for depression severity and other mental conditions, the risk of HDP was significantly higher among women exposed to SNRIs (n = 20; 9.5%) compared to women exposed to SSRIs (n = 72; 5.5%; adjusted odds ratio [aOR] [95% CI] = 2.32 [1.28-4.20]) and to unexposed women (n = 6,224; 4.4%; aOR [95% CI] = 1.89 [1.13-3.18]).Conclusion: This study indicated an increased risk of HDP in women treated with SNRIs versus women treated with SSRIs.
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Hipertensión Inducida en el Embarazo , Inhibidores de Captación de Serotonina y Norepinefrina , Embarazo , Femenino , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Norepinefrina , Serotonina , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Hipertensión Inducida en el Embarazo/inducido químicamente , Hipertensión Inducida en el Embarazo/epidemiologíaRESUMEN
PURPOSE: Fosfomycin trometamol has been recommended as first-line bactericidal antibiotic for urinary tract infections in pregnant women since 2015 in France. However, studies assessing fosfomycin safety in pregnancy are sparse. This study aimed to assess the risk of major Congenital Anomaly (CA) after fosfomycin exposure during the first trimester of pregnancy. METHODS: We performed a comparative study in EFEMERIS, the French database including expecting mothers covered by the French Health Insurance System of Haute-Garonne from July 1st, 2004 to December 31th, 2018. EFEMERIS contains prescribed and dispensed reimbursed medications during pregnancy and pregnancy outcomes. Logistic regressions have been conducted to compare three groups: (1) pregnancies exposed at least once to fosfomycin; (2) pregnancies exposed at least once to nitrofurantoin; and (3) pregnancies exposed neither to fosfomycin nor to nitrofurantoin, another antibiotic prescribed for urinary infections, before and during pregnancy. RESULTS: A total of 2724 (2.0%) pregnant women received at least one fosfomycin prescription during the first trimester, 650 (0.5%) received nitrofurantoin during the first trimester, and 133,502 (97.5%) pregnant women were not exposed to fosfomycin nor to nitrofurantoin. First trimester pregnancy exposure to fosfomycin was not associated with an increased risk of major CA, compared to first trimester exposure to nitrofurantoin (2.0% versus 2.5%; ORa = 0.80 [0.44-1.47]), or to pregnancies unexposed to fosfomycin and nitrofurantoin (2.0% versus 2.1%; ORa = 0.97 [0.73-1.30]). CONCLUSION: This is the first large comparative study assessing fosfomycin safety in pregnancy. It does not exhibit an increased risk of major CA after fosfomycin exposure during the first trimester of pregnancy.
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Fosfomicina , Infecciones Urinarias , Embarazo , Femenino , Humanos , Primer Trimestre del Embarazo , Fosfomicina/efectos adversos , Nitrofurantoína/efectos adversos , Resultado del Embarazo , Antibacterianos/efectos adversos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/epidemiologíaRESUMEN
Pharmacoepidemiological research in pregnant women has focused on adverse drug reactions for the course of pregnancy or for the unborn child, but little is known on the risks for the mother. We reported the results of a study that compared adverse drug reactions in pregnant women with non-pregnant women of childbearing age, and investigated whether which types of adverse reactions were more often reported in pregnant women and which drugs were more often involved. This study was carried out in the French pharmacovigilance database (BNPV). We compared adverse drug reactions reported between 1 January 2010 and 31 December 2019 in pregnant women with those reported in of non-pregnant women of childbearing age. We cross-matched each pregnant woman with three non-pregnant women of childbearing age according to geographic area, age and year the adverse reaction was reported. Data analysis revealed that serious adverse reactions were more frequently reported in pregnant women, including anaphylactic reactions. Other adverse reactions including tachycardia, hypotension and hepatic injury were also more frequent in pregnant women than in non-pregnant women of the same age. This could be explained by physiological changes in pregnancy that lead to greater sensitivity to certain adverse reactions. Some drugs, such as phloroglucinol, metoclopramide, iron, atosiban and nifedipine, were more frequently involved in adverse reactions in pregnant women. These drugs are specifically used during pregnancy, which may explain why they are over-represented in adverse reactions. This is the first comparative descriptive study on drug adverse reactions in pregnant women. Specific epidemiological and pharmacokinetic studies are necessary to confirm these results and better understand the differences observed to improve the monitoring of pregnant women exposed to certain drugs.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Mujeres Embarazadas , Embarazo , Humanos , Femenino , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , FarmacovigilanciaRESUMEN
Background and Objectives: Neuropsychiatric disorders in childhood after prenatal drug exposure raises concerns. Most of the published studies focused on psychotropic medications. This study investigated which prenatal medication exposure was associated with neuropsychiatric disorders in childhood. Methods: A case-control study, nested in the French POMME cohort, was conducted to compare prenatal medication exposure between children with a history of neuropsychiatric care (ages 0-8 years) and children in a control group. POMME included children born in Haute-Garonne to women covered by the general Health Insurance System, between 2010 and 2011 (N = 8,372). Cases were identified through: (1) reimbursement for neuropsychiatric care; (2) psychomotor development abnormalities specified on health certificates; and (3) reimbursement for methylphenidate or neuroleptics. Controls had none of these criteria. Prenatal exposure to each of the major "Anatomical Therapeutic Chemical" classes was compared between the groups. Class(es) for which there was a statistically significant difference (after Bonferroni adjustment, i.e., p < 0.0033) was(were) compared using logistic regression. Results: A total of 723 (8.6%) cases and 4,924 (58.8%) controls were identified. This study showed a statistically significant difference in prenatal exposure to nervous system drugs (excluding analgesics) between the groups [ORa: 2.12 (1.55; 2.90)]. Differences (not statistically significant at the 0.0033 threshold) were also observed for the ATC classes: Musculoskeletal, Genito-urinary System and Sex Hormones, Alimentary Tract and Anti-infectives. Conclusion: Through identification of children with neuropsychiatric disorders and of their prenatal medication exposure, this study provides guidance for the assessment of long-term neuropsychiatric effects after prenatal medication exposure, without focusing on psychotropic medications.
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INTRODUCTION: Topical sertaconazole is indicated in the treatment of vaginal or mucocutaneous fungal infections due to Candida and dermatophytosis. To our knowledge, there is no data available in the literature on the potential effects of sertaconazole during pregnancy. The aim of this study was to evaluate the potential risks of topical sertaconazole use during pregnancy for the foetus and pregnancy. MATERIALS AND METHODS: The EFEMERIS database was used, which contained medications prescribed and dispensed to pregnant women in the Haute-Garonne region whose pregnancy ended between July 2004 and December 2018. We compared pregnant women exposed to sertaconazole at least once during pregnancy to unexposed. Crude and adjusted odds ratios (OR) of major congenital anomalies and small gestational age at birth were estimated using logistic regression models. For other outcomes, hazard ratios (HR) were estimated by Cox regression models. RESULTS: The study included 16,222 pregnant women (15.0%) who were given sertaconazole and 91,976 who were not. Exposure to sertaconazole during pregnancy was not associated with increased risks of any of the investigated outcomes, including natural pregnancy termination (HRa = 0.92 [0.78-1.08]), preterm birth (HRa = 1.06 [0.95-1.17]) and small for gestational age at birth (ORa = 0.78 [0.66-0.92]). No association between risk of major congenital anomalies overall and maternal exposure to sertaconazole during the first trimester was observed (ORa = 1.01 [0.84-1.21]). DISCUSSION: This is the first study involving a large number of pregnant women to assess the potential risks of sertaconazole during pregnancy. This study does not indicate an increased risk of adverse pregnancy outcome and major congenital anomalies from exposure to topical sertaconazole.
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Resultado del Embarazo , Nacimiento Prematuro , Femenino , Humanos , Imidazoles , Recién Nacido , Embarazo , Nacimiento Prematuro/epidemiología , TiofenosRESUMEN
INTRODUCTION: Metopimazine is an anti-emetic drug used to treat nausea and vomiting of pregnancy. However, no animal or clinical data are available regarding its safety in pregnant women. The aim of this study was, therefore, to assess the risk of birth defects and pregnancy loss associated with the use of metopimazine during pregnancy in a population-based cohort study. METHODS: The study focused on the EFEMERIS database including the prescription and dispensation of drugs for pregnant women in Haute-Garonne, France, between July 2004 and December 2017. This was an observational, retrospective, comparative study. Pregnancy loss and major birth defects were compared between women exposed to metopimazine during pregnancy and those with no exposure using multivariate logistic regression and Cox proportional risk models. RESULTS: Among 135,574 pregnant women, 11,402 (8.2%) were exposed to metopimazine during pregnancy, mostly in the first trimester (more than 70% of women). No association was found between major birth defects and exposure to metopimazine in the first trimester of pregnancy (ORa=[95% CI]=1.06 [0.92-1.23]). Pregnancy loss was negatively associated with metopimazine use during pregnancy (HRa [95% CI]=0.80 [0.72-0.88]), taking into account major potential confounders. Comparable rates were recorded between women exposed to metopimazine and those unexposed to the drug in terms of prematurity (6.7% vs. 6.4%), low birth weight (6.2% vs. 6.2%) and small for gestational age (1.2% vs. 1.4%). CONCLUSION: This study illustrates the wide use of metopimazine during pregnancy in France although no studies on efficacy or safety in pregnant women are available. The results of this study do not indicate any teratogenic effect or an increased risk of pregnancy loss of metopimazine.
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Ácidos Isonipecóticos , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
INTRODUCTION: Domperidone is widely used during pregnancy, although the risks associated with pregnant women have not been adequately evaluated. OBJECTIVE: The objective of this study was to compare the rate of pregnancy outcomes and congenital anomalies between pregnant women exposed and unexposed to domperidone during pregnancy. METHODS: We conducted a retrospective cohort study comparing pregnant women exposed and unexposed to domperidone during pregnancy. We used the EFEMERIS database containing the prescriptions and dispensing of drugs to pregnant women in Haute-Garonne, who had a pregnancy outcome between July 2004 and December 2017. We compared pregnant women who were exposed to domperidone at least once during pregnancy to unexposed pregnant women. Logistic regression and Cox proportional risk models were applied. RESULTS: Overall, 13,964 pregnancies (10.3% of pregnancies) were given domperidone. A reduction in the number of pregnant women exposed to domperidone (2004: 17.1% to 2017: 1.2%) was noted. More than 75% of pregnancies were exposed to domperidone in the first trimester of pregnancy. The rate of natural pregnancy termination in pregnant women exposed to domperidone was lower than that in unexposed pregnant women (adjusted hazard ratio = 0.78 [0.71-0.87]). The malformation rate in fetuses/newborns exposed in utero (first trimester) to domperidone is comparable to that of unexposed fetuses/newborns (adjusted odd ratio = 0.89 [0.77-1.03]). CONCLUSIONS: This is the first comparative study to enrol a large number of pregnant women exposed to domperidone. Data regarding the malformation rate following exposure to domperidone during the first trimester of pregnancy are reassuring. Women exposed to domperidone during pregnancy have a decreased risk for natural pregnancy termination, probably owing to an indication bias.
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Anomalías Inducidas por Medicamentos , Aborto Inducido , Anomalías Inducidas por Medicamentos/epidemiología , Anomalías Inducidas por Medicamentos/etiología , Domperidona/efectos adversos , Femenino , Humanos , Recién Nacido , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
BACKGROUND: In France, few data are available on the prescription patterns of antiemetic medications in pregnant women. OBJECTIVES: The purpose of this study was to describe antiemetic medication prescriptions and trends over time. Can we observe significant changes in pregnant woman prescriptions in recent years? METHODS: We conducted a drug utilization study among pregnant women using data from the EFEMERIS database, including 135 574 pregnant women who had a pregnancy outcome between 2004 and 2017 in Haute-Garonne (France). RESULTS: During the study period, 40 028 women (29.5%) received at least one antiemetic prescription during pregnancy. Metoclopramide (56.6%), domperidone (34.9%), and metopimazine (28.5%) were the most commonly prescribed antiemetics, whatever the trimester of pregnancy. Prescriptions of ondansetron only concerned 53 women (0.1%). The prevalence of women who received at least one prescription for an antiemetic decreased from 32.5% in 2010 to 21.6% in 2017. This decline mainly concerned domperidone prescriptions (from 13.1% in 2010 to 1.2% in 2017). Metoclopramide prescriptions also decreased slightly (18.3% in 2010 and 14.0% in 2017). Metopimazine prescriptions increased lowly (8.0% in 2010 and 9.0% in 2017). CONCLUSION: This study showed a decrease of antiemetic prescriptions between 2010 and 2017, linked to the sharp decrease in domperidone use from 2011, probably related to warnings about the risk of cardiovascular adverse effects following exposure to domperidone. We could not observe real switches to other antiemetic medications. No switches to ondansetron could be noted either, with only rare exposure during pregnancy, contrary to other countries, like the United States.
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Antieméticos , Antieméticos/uso terapéutico , Domperidona/efectos adversos , Prescripciones de Medicamentos , Femenino , Francia/epidemiología , Humanos , Embarazo , Mujeres EmbarazadasRESUMEN
PURPOSE: To describe drug prescriptions in pregnant women in France and to identify teratogenic and fetotoxic drug prescriptions. METHODS: This study was carried out using data from Échantillon Généraliste des Bénéficiaires (EGB), a French national health database which includes 1/97th of the French population. Our study population included all pregnant women, aged 10 to 60, who were registered in the EGB and had a pregnancy outcome between 2015 and 2016. Drugs prescribed and dispensed to women during pregnancy and the 3 months before, were collected and described for each year and according to pregnancy trimesters. Prescriptions of major teratogen or fetotoxic drugs were described. RESULTS: We identified 18,279 pregnancies. Among them, 93% received drug prescriptions and dispensations during pregnancy with an average of 7.4±5.5 different drugs. "Alimentary tract and metabolism (75.4%)", "nervous system (64.0%)" and "blood and blood forming organs (58.7%)" classes were the most frequently prescribed to pregnant women. The 5 most frequently prescribed drugs were paracetamol (60.6%), iron (49.2%), folic acid (45.6%), phloroglucinol (44.0%) and colecalciferol (41.4%). The most commonly prescribed drugs included some that have not yet been well evaluated in pregnancy. Prescriptions and dispensations of teratogenic or fetotoxic drugs, as Non-Steroidal Anti-Inflammatory Drugs and retinoids were observed. Valproic acid prescriptions to pregnant women have become extremely rare. CONCLUSION: This descriptive study demonstrates that numerous drugs are prescribed and dispensed to pregnant women in France. These include drugs with a proven teratogenic or fetotoxic effect and many drugs that have not yet been well evaluated in pregnancy.
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Prescripciones de Medicamentos , Mujeres Embarazadas , Femenino , Francia/epidemiología , Humanos , Embarazo , Resultado del Embarazo , Trimestres del EmbarazoRESUMEN
We report cases, registered in the French national pharmacovigilance database, of fetal death and intrauterine growth retardation in women exposed to triptans during pregnancy. Triptans have vasoconstrictive properties and we wonder about their responsibility for these side effects. The use of triptans and other drugs exhibiting vasoconstrictive properties in pregnant women requires a careful benefits/risks evaluation.
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Retardo del Crecimiento Fetal , Triptaminas , Bases de Datos Factuales , Femenino , Humanos , Farmacovigilancia , Embarazo , Triptaminas/efectos adversosRESUMEN
BACKGROUND: Fetal bladder rupture causing urinary ascites is uncommon. It is generally related to invasive fetal medicine procedures or obstructive disorders such as in posterior urethral valves in male fetuses. An exceptional case of spontaneous bladder rupture in a female fetus occurred in a pregnant woman treated with high doses of opiates in an intensive care unit. This unusual obstetric situation leads to discussion of the possible causes of fetal bladder rupture, its management, and the pediatric prognosis. CASE PRESENTATION: We report the case of a 30-year-old nulliparous black woman with a history of mesenteric cystic lymphangioma and multiple bowel resections leading to chronic malabsorption. During her pregnancy, our patient presented with an occlusive syndrome and major bilateral renal dilation. Urinary derivation resulted in iatrogenic bilateral ureteral perforation. Our patient thus presented with major uroperitoneum, bilateral pleural effusion and acute renal failure, treated by thoracic drainage and bilateral nephrostomy. Postoperative pain required treatment with level III analgesics. In this context, 5 days after morphine treatment introduction an enlarged fetal bladder was observed, followed 3 days later by voluminous fetal ascites. The diagnosis of spontaneous bladder rupture was suspected. After multidisciplinary discussion, expectant management was decided. At 31 weeks and 4 days gestation, our patient went into spontaneous labor with a subsequent vaginal delivery. The infant required resuscitation and paracentesis of ascites at birth. Her neonatal course was favorable with a simple urethral bladder drainage. Cystography at day 9 was normal. At 2 years of follow-up, the mother and the child have a normal course. CONCLUSIONS: An iatrogenic origin of megacystis in a female fetus must be evoked in the event of maternal administration of high doses of opiates in the second part of her pregnancy. In our case, the megacystis was followed by spontaneous bladder rupture at 30 weeks of gestation, with a favorable maternal fetal issue.
Asunto(s)
Enfermedades Fetales , Enfermedades de la Vejiga Urinaria , Adulto , Ascitis/etiología , Niño , Femenino , Feto , Humanos , Recién Nacido , Masculino , Embarazo , Rotura Espontánea , Enfermedades de la Vejiga Urinaria/complicaciones , Enfermedades de la Vejiga Urinaria/diagnóstico por imagenRESUMEN
The prevention of relapses and the treatment of depression during pregnancy are difficult challenges. The maintenance of antidepressants in pregnancy with its concomitant risks to mother and child needs to be weighed against those associated with not treating the disease. This study aimed at quantifying the impact of the occurrence of pregnancy on the course of antidepressant treatment among newly treated women (< 6 months). We performed a comparative observational cohort study using the nationwide French reimbursement healthcare system database. Women who conceived in 2014 and initiated an antidepressant at any time in the 6 months before pregnancy were compared with nonpregnant women newly exposed to antidepressants with matching on age, antidepressant exposure, history of psychiatric disorders, and area of residence. The primary outcome was a composite of antidepressant discontinuation, switch to another antidepressant, and concomitant use of antidepressants. The secondary outcome was the resumption of antidepressant during follow-up. We used Cox marginal proportional hazards models to compare time to outcomes between pregnant and nonpregnant women. The pregnant cohort included 6593 women, and the comparison cohort 29,347 nonpregnant women. In the period following the first month of treatment, pregnant women were more likely to experience treatment modification, and especially to stop receiving it, compared with nonpregnant women (adjusted hazard ratio (aHR) 1.58; 95%CI, 1.51-1.62). Pregnant women who discontinued treatment had a 41% decreased incidence of antidepressant resumption compared with nonpregnant women (aHR 0.59; 95%CI, 0.56-0.62). Pregnancy was a determinant of antidepressant treatment modification, and especially of discontinuation.