Effects of maternal modafinil treatment on fetal development and neonatal growth parameters - a multicenter case series of the European Network of Teratology Information Services (ENTIS).

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.

A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France.

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.

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.

Impact of pregnancy on antidepressant treatment course: a population-based comparative cohort study in France.

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.

Antidepressants during pregnancy: a French drug utilisation study in EFEMERIS cohort.

BACKGROUND: Previous studies have suggested that exposure to some antidepressants (AD) during pregnancy could be associated with an increased risk of congenital malformations and neurodevelopment disorders for the child. We conducted a study to describe the use of AD during pregnancy in France. METHODS: We performed a drug utilisation study in EFEMERIS, a French cohort of pregnant women. At the time of the present study, 89,170 pregnant women, who were pregnant from 2005 to 2014 in Haute-Garonne were included. Prevalence and incidence of AD prescriptions during pregnancy, characteristics of AD users, and trends in AD use over the 10-year period were studied. RESULTS: During the 10-year study period, 1620 women registered in EFEMERIS (1.8%) received at least one prescription and dispensation for AD during pregnancy: 1363 during the first (1.5%), 591 during the second (0.7%), and 412 during the third (0.5%) trimester. A total of 2874 women (3.2%) got a prescription for an AD during the 3 months before and/or during pregnancy; 2187 of them (76.1%) stopped AD before pregnancy or during the first trimester. Selective serotonin reuptake inhibitors represented the most prescribed class during pregnancy (1.3%). A very slight decrease in the prevalence of AD prescriptions in pregnant women over time (1.7% in 2014 vs 2% in 2005) and some variations within classes were observed. CONCLUSIONS: Nearly, 2% of women received antidepressant drugs during pregnancy. This assessment encourages following research on these drugs including the potential risk of neurodevelopmental disorders in children after an exposure to antidepressants during pregnancy.

Patterns of antidepressant use during pregnancy: a nationwide population-based cohort study.

AIMS: We explored the patterns of antidepressant use during pregnancy. METHODS: A cohort of women who started a pregnancy in 2014 was identified using data from the French reimbursement healthcare system (covering approximately 99% of the population). Antidepressant usage (initiated before or during pregnancy) was assessed. Explored changes in antidepressant treatment were: associations, switches, discontinuation and resumption of antidepressants during pregnancy. RESULTS: The cohort included 766 508 pregnancies (755 519 women). Antidepressant use during pregnancy was 25.7 per 1000 [95% CI: 25.3-26.0]. New use concerned 3.9 per 1000 [95% CI: 3.7-4.0]; the most initiated class during pregnancy was selective serotonin reuptake inhibitors (SSRIs), while the most prescribed individual drug in second and third trimesters was amitriptyline, a tricyclic. Most changes were observed before pregnancy and during the first trimester: 63% of ongoing treatments in the year before pregnancy were discontinued before conception; 68% of treatments maintained after conception were discontinued during the first trimester; switches or antidepressant associations mostly occurred during the periconceptional period or during the first trimester. Regardless of initial antidepressant, switches to sertraline were the most frequent. Associations mainly consisted of a prescription of tri-/tetracyclic or mirtazapine/mianserin in addition to an SSRI. Discontinuation during pregnancy led to treatment resumption in 22% of pregnancies. CONCLUSIONS: These results suggest that pregnancy was planned or the treatment especially adapted in accordance with existing recommendations in a large proportion of women under antidepressants or in whom such treatments have been initiated after starting a pregnancy.

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.

Prescription of asthma medications before and during pregnancy in France: An observational drug study using the EFEMERIS database.

OBJECTIVE: Asthma affects between 3% to 8% of pregnant women. Previous studies have suggested that women's prescriptions for asthma medications change during pregnancy. The aim was to describe the prescription of asthma medications before and during pregnancy in France. METHODS: Women from the EFEMERIS, a French database assessing the drugs prescribed, dispensed and reimbursed during pregnancy, delivering between July 2004 and December 2012, were included. Women, who were dispensed asthma medications on at least two dates from 3 months prior to pregnancy through delivery, were considered. RESULTS: 2,977 women out of 69,205 (4%) were selected. They were prescribed 2.4 ± 1.2 different anti-asthmatic drugs with 3.5 ± 2.7 different dispensing dates. Almost 62% of the women were dispensed at least one prescription for short-acting ß2-agonist (SABA), 63% at least one inhaled corticosteroid (IC), 42% a fixed-combination of an IC and a long-acting ß2-agonist (LABA) and 8% a LABA. An increase in SABA and IC prescriptions and a decrease in fixed-combination prescriptions were observed during pregnancy compared to pre-pregnancy period. A rapid drop in prescriptions for montelukast was observed. Among the 1,507 women who were prescribed asthma medication before pregnancy, one third had a drop in dispensed asthma medications from the beginning of pregnancy. CONCLUSIONS: The prevalence of dispensed asthma medications varies during pregnancy. There is a decrease in the prescriptions of fixed-combinations during pregnancy and an increase in the prescriptions of ICs. It appears important to study the potential impact of such changes on fetuses and newborns.

Interest of the trajectory method for the evaluation of outcomes after in utero drug exposure: example of anxiolytics and hypnotics.

PURPOSE: The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health. METHODS: The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure. RESULTS: Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR1  = 2.0 [1.0-3.9] and OR2  = 7.6 [2.8-20.5]). CONCLUSIONS: The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd.

[Women's knowledge of folic acid]. / Connaissance des femmes en âge de procréer sur l'acide folique : des progrès à faire !

Many trials have shown that folic acid supplementation before and during pregnancy reduces the risk of neural tube defects in general population. We investigated the knowledge of folic acid in women of child-bearing age. Women of child-bearing age were interviewed by 20 pharmacists living in Haute-Garonne between January and February 2014. One hundred ninety-six women were included in the present study. Out of them, 36% of women never heard of folic acid and 82% were not aware of its benefits. Knowledge was higher in older women, women in a couple and women with higher educational level (P<10-2). This study underlines that women are not enough aware of benefits of folic acid during pregnancy. Moreover, previous studies have shown that French women have low use of folic acid during peri-conceptional period. Information of general population will be required for a better prevention of folic acid-preventable NTDs.

Risk of infections during the first year of life after in utero exposure to drugs acting on immunity: A population-based cohort study.

The aim of the study was to evaluate the association between in utero exposure to drugs that potentially exhibit immunosuppressive activity and occurrence of infections during the first year of life. We conducted a cohort study on the prescription data of pregnant women and their children registered in EFEMERIS cohort (France), during a one-year period. We classified in utero child exposure according to the number of reimbursements for immunosuppressive drugs during pregnancy. The number of infectious episodes during the first year of life was estimated through the number of anti-infective drugs dispensed. The association was estimated by a quasi-Poisson regression with adjustment for confounders. The study population consisted of 9614 children, 3141 of whom had been exposed to immunosuppressive drugs during pregnancy. The most frequently immunosuppressive drugs prescribed were corticosteroids. The mean number of infectious episodes during the first year after birth gradually increased with the number of immunosuppressive drugs dispensed during pregnancy (from 2.38 in controls to 3.88 in the most exposed group). After adjustment for potential confounders, in utero exposure to immunosuppressive drugs was significantly associated with the number of infectious episodes during the first year of life (RR 3ormoreexposuresVS0=1.35, 95% CI 1.24-1.46). Intrauterine exposure to potentially immunosuppressive drugs could be associated with an increased susceptibility to infections in early childhood.

Atropinic burden of drugs during pregnancy and psychological development of children: a cohort study in the EFEMERIS database.

AIM: The aim of this study was to evaluate the potential effect of in utero exposure to drugs with atropinic properties on infant psychological development using atropinic burden (AB) scales. METHODS: Women from the EFEMERIS cohort, a French database including prescribed and dispensed reimbursed drugs during pregnancy and pregnancy outcomes, delivering between 2004 and 2010 were included (n = 43 740). Each drug was classified as having no (score = 0), few (score = 1) or strong (score = 3) atropinic properties. AB per woman was calculated by adding the atropinic scores of drugs prescribed during pregnancy. AB was categorized as exposure or no exposure. Secondary analyses were performed by dividing the exposure into four scores = [0], [1-8], [9-17] and [≥18]. Data for psychological development were extracted from children's medical certificates completed at 9 and 24 months. RESULTS: Thirty-four% (n = 14 925) of women received at least one atropinic drug during pregnancy. Women with AB ≥1 were older and received more drugs during pregnancy than unexposed women. At 24 months, more infants of mothers with AB ≥1 had difficulties to 'name a picture' (ORa , 1.18, 95% CI 1.03, 1.36) and to 'understand instructions' (ORa , 1.61, 95% CI 1.13, , 2.30]) compared with infants of unexposed women. Analyses of four groups of exposure and analyses excluding women receiving psychotropics led to similar results. CONCLUSIONS: The study showed significant association between in utero exposure to drugs with atropinic properties and fewer infant cognitive acquisitions at 24 months. Further exploring the potential effect of simultaneous use of drugs with atropinic effects among pregnant women will bring into consideration whether such prescriptions could be inappropriate for the child.

How to take into account exposure to drugs over time in pharmacoepidemiology studies of pregnant women?

PURPOSE: The aim of this study was to develop a new pharmacoepidemiological method to take into account intensity and evolution of drug exposure, applied to pregnant women. METHODS: Pregnant women were classified according to their drug exposure, in three steps: Conversion of prescription data into exposure variables (using ATC-DDD) Construction of individual trajectories of exposure Clustering of individual trajectories of exposure (using the R package Kml) We applied this method to psychotropic drugs prescribed during pregnancy. The present study involved women, included in the EFEMERIS database, who gave birth in Haute-Garonne (France) between 2004 and 2010 (N = 54 918). RESULTS: Exposure to psychotropic drugs of 3708 pregnant women was studied (6.7%). The pregnant women could be classified into four groups with homogeneous trajectories of exposure: low constant exposure during pregnancy (Cluster A: 70.8% of women); decreasing exposure during the first trimester of pregnancy and low constant exposure thereafter (Cluster B: 19.6%); moderate constant exposure (Cluster C: 8.2%); and high albeit decreasing exposure (Cluster D: 1.4%). CONCLUSIONS: The proposed new method enabled us to describe more precisely women's exposure to drugs during pregnancy, and to distinguish different profiles of exposure. This method could be used to investigate specific outcomes related to duration and intensity of drug exposure during pregnancy, and also to study adverse drug reactions throughout life. Copyright © 2016 John Wiley & Sons, Ltd.

Cyberpharmacovigilance: What is the usefulness of the social networks in pharmacovigilance?

Internet is changing the way people learn about health and illness. Health websites are among the most popular resources on the web. The sharing of patient experiences on a website could be an interesting source of information about adverse drug reactions (ADRs) or could generate "signals". Three examples of the use of patient forums in pharmacovigilance are discussed: (1) analysis of perceptions of risk by patients before and after withdrawal of benfluorex, and then following media coverage; (2) comparison of oral antineoplasic-induced ADRs collected on patient websites with those registered in the French pharmacovigilance database; (3) analysis of data found in the social media about drugs and pregnancy.

Pharmacovigilance, risks and adverse effects of self-medication.

Self-medication means resorting to one or more drugs in order to treat oneself without the help of a doctor. This phenomenon is developing fast. In this review, we will discuss the main definitions of self-medication; we will then present a few important characteristics of this therapeutic practice: prevalence, reasons, populations involved and drugs used. Whilst the theoretical risks of self-medication have been abundantly discussed in the literature (adverse effects, interactions, product, dosage or treatment duration errors, difficulty in self-diagnosis, risk of addiction or abuse…), there is in fact very little detailed pharmacovigilance data concerning the characteristics and the consequences of this usage in real life. This study therefore describes the all too rare data that is available: patients, clinical characteristics, "seriousness" and drugs involved in the adverse effects of self-medication. It also discusses leads to be followed in order to minimize medication risks, which are obviously not well known and clearly not sufficiently notified.

Which pharmacovigilance for vaccines?

Vaccines are drugs. Like all medicines, they are submitted to pre-clinical tests and then clinical trials. These tests and trials are essential but unfortunately insufficient because, for example, they are necessarily too short, they include too few subjects not representative of future treated patients... These points underline, once again, the importance for both patients and their doctors of the pharmacovigilance after marketing authorization. Phar- macovigilance of vaccines involves first, like all other medicines, the reporting of adverse drug reactions to the regional pharmacovigilance centers. For vaccines, it can be first spontaneous (i.e. not solicited or passive) and sought (encouraged active, as did for the HIN vaccine) involving not only health professionals but also the whole population (patients, relatives... ). Spontaneous reporting remains the only methodfor an early warning detection. The pharmacoepidemiological methods (case-control, cohort studies, expected- observed method, Self Controlled Cases-Series...) are secondarily used to confirm or deny a signal suggested by spontaneous notifications. More than elsewhere, these studies are also needed to quantify the populational risk. Pharmacovigilance is essential for a modern, clinical and medical evaluation of the benefit of vaccine. Knowledge of vaccine pharmaco- vigilance data also allows to recall the excellent benefits harms balance of these drugs, much higher than that of many other drug classes.

Investigation of the putative associations between dairy consumption and incidence of type 1 and type 2 diabetes.

A growing body of evidence suggests a possible relationship between the consumption of dairy products and the incidence of diabetes. A positive correlation between the early introduction of dairy in infancy and the incidence of type 1 diabetes (T1D) in genetically predisposed infants has been suggested by studies on rodents and humans. However, the lines of evidence supporting this association, including epidemiological studies and the observation of antibodies to bovine serum albumin, ß-casein and bovine insulin in the serum of patients with T1D, are not without controversy. On the other hand, an inverse relationship between the consumption of dairy foods and the development of metabolic syndrome and/or type 2 diabetes (T2D) has been implied by epidemiological studies. Several dairy components, especially milk proteins, are believed to play a role in the beneficial effect of dairy consumption on glucose regulation by modulation of incretin hormones. Other dietary factors have also been associated with the incidence of T1D and T2D, indicating that dairy foods might be only one among many dietary agents possibly implicated in the development of diabetes. The present paper critically reviews the evidence and plausible mechanisms for the putative associations between dairy food consumption and incidence of T1D and T2D.

Drug-induced adverse reactions via breastfeeding: a descriptive study in the French Pharmacovigilance Database.

PURPOSE: Most drugs are excreted in maternal milk and may therefore be ingested by children during breastfeeding. Data concerning the safety of the use of drugs by breastfeeding women are patchy, and almost nothing is known about this issue for many drugs. METHODS: The aim of this study was to describe the adverse drug reactions of drugs transmitted in breast milk on the basis of the data collected in the French Pharmacovigilance Database. All spontaneous reports of adverse drug reactions (ADRs) in breastfed infants recorded in the National Pharmacovigilance Database by the 31 French regional pharmacovigilance centres between 1984 and June 2011 were investigated. RESULTS: Between January 1985 and June 2011, 276 adverse drug reactions in 174 breastfed children were notified to the French Pharmacovigilance Network. The most frequently reported adverse drug reactions were neurological (28.6 %) and gastrointestinal (20.3 %). Sixty-five of the adverse drug reactions recorded were considered to be serious (37.4 %). The results of our study confirm that certain drugs were frequently implicated in serious adverse drug reactions. Two cases of ADRs (1.1 %) had a 'certain' causality score (I4) and 13 (7.5 %) a 'likely' score (I3). The suspected drugs include antiepileptic drugs, opiate analgesics and benzodiazepines. These results also demonstrate that some drugs that were thought to be anodyne or for which no data were available, such as ketoprofen and hydroxyzine, may be implicated in adverse effects. Finally, these data show that certain drugs, like pseudoephedrine, which should not be used during breastfeeding, were nevertheless implicated in several of the adverse drug reactions recorded. CONCLUSION: This study shows that ADR via breastfeeding are rarely reported due to low awareness or low occurrence of ADR via breast milk. These results highlight the need for additional pharmacokinetic, clinical and epidemiological studies, given the paucity of published data. They also demonstrate the need to improve information for the general public about drugs and self-medication during breastfeeding.

Analysis of chats on French internet forums about drugs and pregnancy.

PURPOSE: Some pregnant women use the internet to search for medical information. However, online information is not controlled. The objectives were to describe French online chats about drugs and pregnancy and evaluate the quality and reliability of information shared by internet users. METHODS: This French descriptive study was performed in November 2012. In order to identify drugs and pregnancy-related forum websites, we used three French key words: forum, pregnancy and drug. We explored the first 10 websites from the search result. Diseases were described using the International Classification of Diseases and drugs classified with the Anatomical Therapeutic Chemical codes and the FDA risk classification. RESULTS: We selected 115 questions that were mainly posted by pregnant internet users in French forums. Drugs raising questions were mostly "nervous system," "anti-infective for systemic use" and "respiratory system" drugs. The risk during pregnancy for nearly half of these drugs had not been evaluated properly. Health professionals were only involved in 7% of the 214 answers. Internet users advised to take a drug in 21% of their answers. Thirty-four percent of those recommended drugs had not been well-evaluated or were potentially at risk during pregnancy. Finally, 12% of the answers could be at risk for pregnant woman. CONCLUSIONS: This study shows that information related to drugs and pregnancy in online chats could be at risk for pregnant women. Internet users must be aware that online forums are not reliable sources of information.