Exposure to Non-Steroidal Anti-Inflammatory Drugs during Pregnancy and the Risk of Selected Birth Defects: A Prospective Cohort Study

Contains fulltext : 97906.pdf (publisher's version ) (Open Access)BACKGROUND: Since use of non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy is common, small increases in the risk of birth defects may have significant implications for public health. Results of human studies on the teratogenic risks of NSAIDs are inconsistent. Therefore, we evaluated the risk of selected birth defects after prenatal exposure to prescribed and over-the-counter NSAIDs. METHODS AND FINDINGS: We used data on 69,929 women enrolled in the Norwegian Mother and Child Cohort Study between 1999 and 2006. Data on NSAID exposure were available from a self-administered questionnaire completed around gestational week 17. Information on pregnancy outcome was obtained from the Medical Birth Registry of Norway. Only birth defects suspected to be associated with NSAID exposure based upon proposed teratogenic mechanisms and previous studies were included in the multivariable logistic regression analyses. A total of 3,023 women used NSAIDs in gestational weeks 0-12 and 64,074 women did not report NSAID use in early pregnancy. No associations were observed between overall exposure to NSAIDs during pregnancy and the selected birth defects separately or as a group (adjusted odds ratio 0.7, 95% confidence interval 0.4-1.1). Associations between maternal use of specific types of NSAIDs and the selected birth defects were not found either, although an increased risk was seen for septal defects and exposure to multiple NSAIDs based on small numbers (2 exposed cases; crude odds ratio 3.9, 95% confidence interval 0.9-15.7). CONCLUSIONS: Exposure to NSAIDs during the first 12 weeks of gestation does not seem to be associated with an increased risk of the selected birth defects. However, due to the small numbers of NSAID-exposed infants for the individual birth defect categories, increases in the risks of specific birth defects could not be excluded

Epidemiology of pre-existing multimorbidity in pregnant women in the UK in 2018: a population-based cross-sectional study

BACKGROUND: Although maternal death is rare in the United Kingdom, 90% of these women had multiple health/social problems. This study aims to estimate the prevalence of pre-existing multimorbidity (two or more long-term physical or mental health conditions) in pregnant women in the United Kingdom (England, Northern Ireland, Wales and Scotland). STUDY DESIGN: Pregnant women aged 15-49 years with a conception date 1/1/2018 to 31/12/2018 were included in this population-based cross-sectional study, using routine healthcare datasets from primary care: Clinical Practice Research Datalink (CPRD, United Kingdom, n = 37,641) and Secure Anonymized Information Linkage databank (SAIL, Wales, n = 27,782), and secondary care: Scottish Morbidity Records with linked community prescribing data (SMR, Tayside and Fife, n = 6099). Pre-existing multimorbidity preconception was defined from 79 long-term health conditions prioritised through a workshop with patient representatives and clinicians. RESULTS: The prevalence of multimorbidity was 44.2% (95% CI 43.7-44.7%), 46.2% (45.6-46.8%) and 19.8% (18.8-20.8%) in CPRD, SAIL and SMR respectively. When limited to health conditions that were active in the year before pregnancy, the prevalence of multimorbidity was still high (24.2% [23.8-24.6%], 23.5% [23.0-24.0%] and 17.0% [16.0 to 17.9%] in the respective datasets). Mental health conditions were highly prevalent and involved 70% of multimorbidity CPRD: multimorbidity with ≥one mental health condition/s 31.3% [30.8-31.8%]). After adjusting for age, ethnicity, gravidity, index of multiple deprivation, body mass index and smoking, logistic regression showed that pregnant women with multimorbidity were more likely to be older (CPRD England, adjusted OR 1.81 [95% CI 1.04-3.17] 45-49 years vs 15-19 years), multigravid (1.68 [1.50-1.89] gravidity ≥ five vs one), have raised body mass index (1.59 [1.44-1.76], body mass index 30+ vs body mass index 18.5-24.9) and smoked preconception (1.61 [1.46-1.77) vs non-smoker). CONCLUSION: Multimorbidity is prevalent in pregnant women in the United Kingdom, they are more likely to be older, multigravid, have raised body mass index and smoked preconception. Secondary care and community prescribing dataset may only capture the severe spectrum of health conditions. Research is needed urgently to quantify the consequences of maternal multimorbidity for both mothers and children

Women’s beliefs about medicines and adherence to pharmacotherapy in pregnancy: Opportunities for community pharmacists?

Background During pregnancy women might weigh benefits of treatment against potential risks to the unborn child. However, non-adherence to necessary treatment can adversely affect both mother and child. To optimize pregnant women’s beliefs and medication adherence, community pharmacists are ideally positioned to play an important role in primary care. Objective This narrative review aimed to summarize the evidence on 1) pregnant women’s beliefs, 2) medication adherence in pregnancy, and 3) community pharmacists’ counselling during pregnancy. Method Three search strategies were used in Medline and Embase to find original studies evaluating women’s beliefs, medication adherence and community pharmacists’ counselling during pregnancy. All original descriptive and analytic epidemiological studies performed in Europe, North America and Australia, written in English and published from 2000 onwards were included. Results We included 14 studies reporting on women’s beliefs, 11 studies on medication adherence and 9 on community pharmacists’ counselling during pregnancy. Women are more reluctant to use medicines during pregnancy and tend to overestimate the teratogenic risk of medicines. Risk perception varies with type of medicine, level of health literacy, education level and occupation. Furthermore, low medication adherence during pregnancy is common. Finally, limited evidence showed current community pharmacists’ counselling is insufficient. Barriers hindering pharmacists are insufficient knowledge and limited access to reliable information. Conclusion Concerns about medication use and non-adherence are widespread among pregnant women. Community pharmacists’ counselling during pregnancy is insufficient. Further education, training and research are required to support community pharmacists in fulfilling all the opportunities they have when counselling pregnant women

Ibuprofen results in alterations of human fetal testis development

International audienceAmong pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10-12 GW, or in second trimester xenografted testes (14-17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow 'early window' of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology

COVID-19 in pregnancy-what study designs can we use to assess the risk of congenital anomalies in relation to COVID-19 disease, treatment and vaccination?

BACKGROUND: The COVID-19 pandemic has accelerated pregnancy outcome research, but little attention has been given specifically to the risk of congenital anomalies (CA) and first trimester exposures. OBJECTIVES: We reviewed the main data sources and study designs used internationally, particularly in Europe, for CA research, and their strengths and limitations for investigating COVID-19 disease, medications and vaccines. POPULATION: We classify research designs based on four data sources: a) spontaneous adverse event reporting, where study subjects are positive for both exposure and outcome, b) pregnancy exposure registries, where study subjects are positive for exposure, c) congenital anomaly registries, where study subjects are positive for outcome and d) population healthcare data where the entire population of births is included, irrespective of exposure and outcome. STUDY DESIGN: Each data source allows different study designs, including case series, exposed pregnancy cohorts (with external comparator), ecological studies, case-control studies and population cohort studies (with internal comparator). METHODS: The quality of data sources for CA studies is reviewed in relation to criteria including diagnostic accuracy of CA data, size of study population, inclusion of terminations of pregnancy for foetal anomaly, inclusion of first trimester COVID-19-related exposures and use of an internal comparator group. Multinational collaboration models are reviewed. RESULTS: Pregnancy exposure registries have been the main design for COVID-19 pregnancy studies, but lack detail regarding first trimester exposures relevant to CA, or a suitable comparator group. CA registries present opportunities for improving diagnostic accuracy in COVID-19 research, especially when linked to other data sources. Availability of inpatient hospital medication use in population healthcare data is limited. More use of ongoing mother-baby linkage systems would improve research efficiency. Multinational collaboration delivers statistical power. CONCLUSIONS: Challenges and opportunities exist to improve research on CA in relation to the COVID-19 pandemic and future pandemics

ACUTE RELEASE OF CATECHOLAMINES ON CIRCULATING BLOOD CELL ADRENOCEPTORS AND METABOLIC INDICES IN DOG

International audienceThe effects of acute release of endogenous catecholamines on both platelet alpha 2 and leukocyte beta adrenoreceptors and metabolic indices (glucose and free fatty acids) were investigated in dogs by means of a model of neurogenic hypertension following acute sinoaortic denervation (ASAD). Despite the marked increase in catecholamine levels (+4.2-fold for noradrenaline and 16.7-fold for adrenaline, for example, at minute 45 following ASAD) and in glucose plasma levels, and the significant decrease in free fatty acid plasma levels, no change in platelet alpha 2 or leukocyte beta adrenoreceptor binding sites (number as well as affinity) was observed during the whole experiment. It is suggested that the number of platelet alpha 2- and leukocyte beta-adrenoreceptors is not submitted to short-term regulation, at least by endogenous catecholamines in dogs

Falsified or forged medical prescriptions as an indicator of pharmacodependence: a pilot study. Community pharmacists of the Midi-Pyrenees

OBJECTIVE: While data on drug abuse liability have been determined for selected drugs in experimental studies, there is limited information available about drug abuse in real life. This study presents the results of a simple experimental epidemiologic survey of prescription forgeries in community pharmacies in the Midi-Pyrenees area (southwest France). During four periods (September-October 1991, January-June 1992, September-October 1992 and January-June 1993), resident pharmacy students in several volunteer pharmacies were asked to complete a specific report form for each suspect prescription request. The main criteria used to identify forgeries were: inadequate dosage, multiple use of the prescription form, drafting not in accordance with the rules of prescription or false prescription forms (stolen prescription forms, photocopies). RESULTS: A total of 165 falsified prescriptions were collected. The 305 drugs involved in these forged prescriptions were opiate analgesics, benzodiazepines, amphetamines and minor opiate analgesics. Medications were essentially buprenorphine, flunitrazepam (in 2 mg dosage), phenobarbitone+amphetamine and chlorazepate. CONCLUSION: These results suggest that forged prescriptions can be used as an indicator of potential abuse liability of marketed psychoactive drugs. Although this survey cannot describe the real prevalence of the misuse or abuse of drugs, it constitutes a useful warning epidemiologic system to elicit early observations regarding new misuses of drugs as they are requested at the pharmacy

Eur Arch Psychiatry Clin Neurosci

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