First trimester pregnancy exposure to fosfomycin and risk of major congenital anomaly: a comparative study in the EFEMERIS database.

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.

Topical sertaconazole during pregnancy and risk of adverse pregnancy outcome and major congenital anomalies: Comparative study in the EFEMERIS database.

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.

Pregnancy outcomes in women exposed to cancer chemotherapy.

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.

Ergot and non-ergot dopamine agonists and heart failure in patients with Parkinson's disease.

PURPOSE: Some studies have suggested a potential risk of heart failure in patients with Parkinson's disease receiving dopamine (DA) agonists. However, the results are conflicting. We used VigiBase®, the World Health Organization (WHO) Global Individual Case Safety Reports (ICSRs) database, to investigate a potential signal strengthening of heart failure with DA agonists in Parkinsonian patients older than 45 years. METHODS: A case/non-case (disproportionality) analysis was performed in Vigibase® using ICSRs registered between 1978 and May 2016. The signal of disproportionality was calculated using reporting odds ratios (ROR). In our study, 154 ICSRs of heart failure occurring in 154 Parkinsonian patients (mean age 69.6 years, 51 % women) treated with DA agonists were included. RESULTS AND CONCLUSION: There was a significant signal between occurrence of heart failure and exposure to pergolide or cabergoline in particular and ergot derivatives in general. In contrast, none signal was found for rotigotine, pramipexole, apomorphine, or ropinirole in particular and non-ergot derivatives in general. The present study underlines the importance to prescribe as DA agonists in Parkinsonian patients only non-ergot derivatives, excluding ergot drugs.

What are the links between maternal social status, hippocampal function, and HPA axis function in children?

The association of parental social status with multiple health and achievement indicators in adulthood has driven researchers to attempt to identify mechanisms by which social experience in childhood could shift developmental trajectories. Some accounts for observed linkages between parental social status in childhood and health have hypothesized that early stress exposure could result in chronic disruptions in hypothalamic-pituitary-adrenal (HPA) axis activation, and that this activation could lead to long-term changes. A robust literature in adult animals has demonstrated that chronic HPA axis activation leads to changes in hippocampal structure and function. In the current study, consistent with studies in animals, we observe an association between both maternal self-rated social status and hippocampal activation in children and between maternal self-rated social status and salivary cortisol in children.

Risk of Hypertensive Disorders of Pregnancy in Women Treated With Serotonin-Norepinephrine Reuptake Inhibitors: A Comparative Study Using the EFEMERIS Database.

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.

Prenatal Drug Exposure in Children With a History of Neuropsychiatric Care: A Nested Case-Control Study.

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.

Initial data on the safety of metopimazine during pregnancy and the risk of major birth defects and pregnancy loss - An observational study using the EFEMERIS database.

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.

What changes in prescription patterns of antiemetic medications in pregnant women in France?

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.

Drug prescriptions in French pregnant women between 2015 and 2016: A study in the EGB database.

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.

Risk of Pregnancy Termination and Congenital Anomalies After Domperidone Exposure: A Study in the EFEMERIS Database.

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.

Functional outcome after severe childhood traumatic brain injury: Results of the TGE prospective longitudinal study.

BACKGROUND: Childhood severe traumatic brain injury (TBI) is a leading cause of long-lasting acquired disability, but little is known about functional outcome. OBJECTIVE: We aimed to 1) study clinical recovery and functional outcome over 24 months after severe childhood TBI, 2) identify early sociodemographic and severity factors influencing outcome, and 3) examine the clinical utility of the Pediatric Injury Functional Outcome Scale (PIFOS) to assess functional outcome. METHODS: Children (0-15 years) consecutively admitted in a trauma centre after accidental severe TBI over 3 years were included in a prospective longitudinal study (Traumatisme Grave de l'Enfant cohort). We measured clinical/neurological recovery, functional status (Pediatric Injury Functional Outcome Scale, [PIFOS]), overall disability (pediatric Glasgow Outcome Scale [GOS-Peds]) as well as intellectual ability (Wechsler scales) and educational outcome (mainstream school vs special education) of survivors at 1, 3, 12 and 24 months post-injury. RESULTS: For 45 children (aged 3 to 15 years at injury), functional impairments were severe within the first 3 months. Despite the initial rapid clinical recovery and significant improvement over the first year, substantial alterations persisted for most children at 12 months post-TBI, with no significant improvement up to 2 years. Up to 80% of children still had moderate or severe overall disability (GOS-Peds) at 24 months. The severity of functional impairments (PIFOS) at 12 and 24 months was mostly related to socio-emotional, cognitive and physical impairments, and was significantly correlated with clinical/neurological deficits and cognitive (intellectual, executive) and behavioural disorders. Initial TBI severity was the main prognostic factor associated with functional status over the first 2 years post-injury. CONCLUSIONS: Our results confirm the significant impact of severe childhood TBI on short- and medium-term functional outcomes and overall disability. All patients should benefit from systematic follow-up. The PIFOS appeared to be an accurate and reliable tool to assess functional impairment evolution and clinically meaningful outcomes over the first 2 years post-injury.

Higher intake of medications for digestive disorders in children prenatally exposed to drugs with atropinic properties.

Childhood digestive disorders are a common occurrence and are sometimes unexplained. Maternal medication during the development of the foetus' digestive system may contribute to the increase in childhood digestive disorders, especially with drugs acting on the cholinergic system. This study investigated the association between prenatal exposure to drugs with atropinic properties and the use of digestive disorder medications in childhood (0-3 years). Children from POMME (PrescriptiOn Médicaments Mères Enfants), a French database of reimbursed drugs for pregnant women and their children, were included (N = 8 372). Each drug prescribed during antenatal life was assigned an atropinic score (0 = null, 1 = low, 3 = strong). The prenatal atropinic burden was calculated as the sum of atropinic scores of drugs prescribed. More than 30% (N = 2 652) of the children were prenatally exposed to atropinic drugs. They used significantly more digestive disorder medications than unexposed children (RRa = 1.11 [1.06; 1.16]). The strength of the association increased with the prenatal atropinic burden. Our results suggest long-term digestive effects after prenatal exposure to atropinic drugs.

POMME: The New Cohort to Evaluate Long-Term Effects After Prenatal Medicine Exposure.

INTRODUCTION: The POMME (PrescriptiOn Médicaments Mères Enfants) cohort has been implemented for the evaluation of the long-term consequences of medicine prenatal exposure. It holds anonymous medical information as well as information on medicine and healthcare reimbursement to the children, from the first day of intra-uterine life until childhood. OBJECTIVE: This article provides a description of the cohort regarding its structure and content and presents an outlook of the studies that could be performed with this new data source. METHODS: Data sources include (1) the French Health Insurance Database (medicines and medical care prescriptions and reimbursements to children and mothers during pregnancy) and (2) the Mother and Child Protection Centre Database (child health certificates at birth, 9 months of age and 24 months of age). Children born in Haute-Garonne (south-west France), over a period of 1 year (from 1 July to 30 June), are registered in POMME every 5 years. The cohort began on 1 July, 2010. RESULTS: To date, 8372 children have been recorded in POMME. They have reached 7 years of age now. Among them, 4249 (50.8%) are boys, 286 (3.4%) were from multiple pregnancies and 519 (6.2%) were born prematurely. They were prenatally exposed to 9.8 ± 6.1 medications. After birth, drug exposure was greatest in children aged 0-2 years. Children were mostly exposed to paracetamol, anti-infective agents and respiratory system drugs; 908 (10.8%) children presented with at least two signs of psychomotor development disorders. CONCLUSIONS: POMME provides an observatory study on drug exposure and medical care use in children. This innovative cohort would make it possible to assess the risk of the long-term consequences of prenatal medicine exposure.

Pharmacoepidemiology in pregnancy.

Taking a medication is usually a challenge for a pregnant woman as the beneficial drug effect on the mother has to be considered regarding its potential adverse effects, not only for her but also for her unborn child. As medication use is common in pregnant women, by chance or necessity, it gives the opportunity to evaluate the consequences of prenatal drug exposure in real life through pharmacoepidemiological studies. This paper provides an overview of data sources, study designs and data analysis methods that can be used for pregnancy medication safety studies. In the future, the implementation of responsive international networks may be the keystones of drug evaluation in pregnancy.

Non-steroidal anti-inflammatory drug prescriptions from the 6th month of pregnancy: impact of advice from health authorities.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. On June 2008 and February 2009, Dear Doctor Letters (DDLs) were sent by the French Health Authorities (AFSSAPS) to remind practitioners of risks with NSAIDs after the fifth month of pregnancy. The aim of this study was to evaluate the impact of these letters on NSAID prescriptions during late pregnancy. EFEMERIS is a French database that registers drugs prescribed and reimbursed during pregnancy and outcomes between 2004 and 2015. We performed a descriptive study and a 'before-and-after' comparison of NSAID prescriptions between 3 June 2006 and 3 June 2008 ('before group'), and between 1 March 2010 and 1 March 2012 ('after group'). We carried out a Cochran Armitage trend test to check whether the rate of women exposed to NSAIDs varies linearly over time. We identified 948 (4.38%) pregnant women in the 'before group' and 678 (2.73%) in the 'after group' receiving at least one NSAID prescription in late pregnancy (P < 0.0001). Between 2006 and 2012, mainly prescriptions for morniflumate/niflumic acid (1.7% vs. 0.9%; P < 0.0001), ibuprofen (0.8% vs. 0.6%; P = 0.01) and ketoprofen (0.7% vs. 0.3%; P < 0.0001) fell significantly after DDLs. The Cochran Armitage trend test shows that the percentage of women exposed to NSAIDs in late pregnancy decreased significantly during the study period (P < 0.0001). This study highlighted a significant decrease in the percentage of women receiving NSAID prescriptions during late pregnancy after DDLs. This decrease is not linked to a specific women's profile or prescriber's medical discipline.

In utero drug exposure and hearing impairment in 2-year-old children A case-control study using the EFEMERIS database.

INTRODUCTION: As the ear development extends from the 4th to the 30th week of pregnancy, in utero exposure to ototoxic drugs might lead to hearing impairment in the fetus. The main study objective was to assess the association between in utero drug exposure and the occurrence of hearing impairment in 2-year-old children. METHODS AND MATERIALS: A case-control study was carried out using the EFEMERIS database, recording medications dispensed during pregnancy and the compulsory health certificates for child at 8 days, 9 and 24 months. Cases were defined as children with an abnormal hearing examination recorded on the 24-month certificate and controls as children with a normal hearing examination. Exposure was defined as at least one prescription and dispensation to the mother of drugs grouped at the 3rd level of the Anatomical Therapeutic and Chemical Classification level, compared to no exposure. Univariate logistic regressions were carried out. If the 95% confidence interval (95% CI) of the odds ratio (OR) was significant, a multivariable logistic regression was performed, adjusted on confounders. RESULTS: A total of 1,245 cases with abnormal hearing evaluation and 28,046 controls were selected for analysis. Case and control mothers were comparable in terms of age, education and congenital infection. Cases and controls were comparable in terms of prematurity, asphyxia and weight at birth. However, among cases (versus controls), there were more ear deformities (0.6% vs 0.0% p≤0.001), and more recurring otitis (11.3% vs 5.3% p≤0.0001). When adjusted on confounders, the following drugs remained significant versus no exposure: acetylsalicylic acid at low dosage (OR 95% CI 1.61 [1.09-2.37]), valproic acid or valpromide (OR 95% CI 5.20 [1.93-14.00]), systemic corticosteroids (OR 95% CI 0.75 [0.61-0.93]. In a sensitivity analysis which excluded children with recurrent otitis at 24 months, these three results remained significant. CONCLUSIONS: This is the first study evaluating the risk of hearing disorders due to in utero exposure to drugs. Hearing loss was associated with valproic acid and low-dose acetylsalicylic acid exposure during pregnancy. Conversely, children with normal hearing were more likely to have been exposed in utero to corticosteroids than children with hearing loss.

Atropinic (anticholinergic) burden in antipsychotic-treated patients.

Antipsychotic drugs possess side atropinic (anticholinergic) properties that may induce several adverse drug reactions (ADRs), such as memory loss or cognitive impairment. The aim of this study was to investigate anticholinergic burden in patients treated with antipsychotic drugs. All ADR reports including at least one antipsychotic and registered between 2000 and 2015 in the Midi-Pyrénées PharmacoVigilance Database were extracted and analyzed using the Anticholinergic Duran's list. The primary objective of this cross-sectional study was to calculate anticholinergic burden in antipsychotic-treated patients; the secondary one was to investigate associated factors. Among the 1948 reports, the average number of atropinic drugs per report was 2.4 ± 1.4. At least one atropinic drug was found in 59.4% of reports (1158), in addition to antipsychotic drugs. The mean anticholinergic burden per report was 3.9 ± 2.9. A value ≥3 was found in 61.7% of the reports. A significant association between anticholinergic burden, age, and male gender of patients was found. The mean value of anticholinergic burden remained stable during the study period. This study showed high values of anticholinergic burden in patients receiving antipsychotics. Thus, considering the potential noxious clinical impact of atropinic properties on cognitive functions, an appropriate approach should be used to reduce prescription of antipsychotics with a high anticholinergic burden but also coprescription of other frequently associated atropinic drugs, such as antiparkinsonians, H1 antihistamines, or imipraminic antidepressants in these patients.

Contextual determinants of participation in cervical cancer screening in France, 2010.

BACKGROUND: Some contextual factors associated with participation in cervical cancer screening are reported in the literature, but few studies have examined their combined effect. Our objective was to assess the role of contextual characteristics, separately and in combination, in participation in cervical cancer screening in France. METHODS: Marginal Poisson regression models - taking into account the correlation between women in a given commune - were conducted using data from the Baromètre Santé 2010 survey. The characteristics of the commune of residence of the women studied were the potential spatial accessibility to general practitioners (GP) and gynecologists, the agglomeration category, and the socioeconomic level. RESULTS: The analyses were performed in 3380 women, 88.2% of whom were up to date with their cervical cancer screening. Once the individual characteristics were taken into account, the screening participation rate was similar in all the communes, with the exception of those with poor access to a gynecologist and good access to a GP, where the rate was 6% lower (95%CI: 0.5-11%) than in the communes with good access to both GP and gynecologist. The same association with accessibility was observed in small agglomerations. Compared to women living in the more advantaged communes, the screening participation rate was 8% (2-12%) lower in those living in the more disadvantaged ones, except when accessibility to both types of physician was high. DISCUSSION: We observed an association between potential spatial accessibility to care in women's residential communities and their cervical cancer screening practices, in particular in small agglomerations, rural communes, and more disadvantaged communes.

A comparative study of QT prolongation with serotonin reuptake inhibitors.

BACKGROUND: QT interval prolongations were described with citalopram and escitalopram. However, the effects of the other serotonin reuptake inhibitors (SRIs) remained discussed. In order to identify a putative signal with other SRIs, the present study investigates the reports of QT interval prolongation with SRIs in two pharmacovigilance databases (PVDB). METHODS: Two kinds of investigations were performed: (1) a comparative study in VigiBase®, the WHO PVDB, where notifications of QT prolongation with six SRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) were selected. Cases with overdose or pregnancy were excluded. The relationship between the "suspected" SRI and occurrence of QT prolongation was assessed by calculating reporting odds ratio (ROR) in a case/non-case design. (2) A descriptive study of QT prolongation reports with citalopram and escitalopram in the French FPVD. RESULTS: In VigiBase®, 855 notifications were identified (mean age 56.2 years, mainly women 73%). Among them, 172 (20.1%) were associated to escitalopram; 299 (35.0%), to citalopram; 186 (21.8%), to fluoxetine; 94 (11.0%), to sertraline; 66 (7.7%), to paroxetine; and 38 (4.4%) to fluvoxamine. A significant ROR value (higher than 1) was only found for citalopram (3.35 CI95% [2.90-3.87]) or escitalopram (2.50 [2.11-2.95]). In the FPVD, eight reports of QT prolongation were found with citalopram and 27 with escitalopram, mainly in women (77.1%) with a mean age of 73.2 years. In 23 cases (66%), SRIs were associated with other suspected drugs, mainly cardiotropic or psychotropic ones. Hypokalemia was associated in six patients. CONCLUSION: This study, performed in real conditions of life, shows a clear signal of QT prolongation with only two SRIs, citalopram and escitalopram, indicating that QT prolongation is not a SRI class effect.