Abstract:
OBJECTIVE:To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children. DESIGN:Population based cohort study. SETTING:The UK Clinical Practice Research Datalink. PARTICIPANTS:The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort. MAIN OUTCOME MEASURES:Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder. RESULTS:Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses. CONCLUSIONS:Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available. TRIAL REGISTRATION:ClinicalTrials.gov NCT03948620.
journal_name
BMJjournal_title
BMJ (Clinical research ed.)authors
Fan H,Gilbert R,O'Callaghan F,Li Ldoi
10.1136/bmj.m331subject
Has Abstractpub_date
2020-02-19 00:00:00pages
m331eissn
0959-8138issn
1756-1833journal_volume
368pub_type
杂志文章abstract:OBJECTIVE:To investigate whether users of oral contraceptives and in [corrected] carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. DESIGN:Comparison of a prospective series of cases of cerebral sinu...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.316.7131.589
更新日期:1998-02-21 00:00:00
abstract::Research in general practice is becoming increasingly popular, and most general practitioners will sooner or later have to decide whether to become involved with clinical trials sponsored by drug companies. This paper outlines the advantages and disadvantages of multicentre research--based on experience of running a r...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.307.6915.1331
更新日期:1993-11-20 00:00:00
abstract:OBJECTIVE:To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut. DESIGN:Natural experiment comparing two fixed cohorts from 1987 to 1997. SETTING:Seattle-Puget Sound and Connecticut...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,多中心研究
doi:10.1136/bmj.325.7367.740
更新日期:2002-10-05 00:00:00
abstract:OBJECTIVES: To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Conge...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,多中心研究
doi:10.1136/bmj.i4721
更新日期:2016-09-13 00:00:00
abstract:OBJECTIVE:To investigate the relations of maternal diet and smoking during pregnancy to placental and birth weights at term. DESIGN:Prospective cohort study. SETTING:District general hospital in the south of England. PARTICIPANTS:693 pregnant nulliparous white women with singleton pregnancies who were selected from ...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.319.7206.339
更新日期:1999-08-07 00:00:00
abstract:OBJECTIVE:To assess the efficacy of high serum cholesterol concentration, raised blood pressure, and smoking as predictors of coronary heart disease. DESIGN:Prospective cohort study of middle aged men conducted over 25 years. SETTING:Finish components of an ongoing international study (seven countries study). PARTIC...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.299.6691.81
更新日期:1989-07-08 00:00:00
abstract:OBJECTIVE:To test whether the relation between income inequality and mortality found in US states is because of different levels of formal education. DESIGN:Cross sectional, multiple regression analysis. SETTING:All US states and the District of Columbia (n=51). DATA SOURCES:US census statistics and vital statistics...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.324.7328.23
更新日期:2002-01-05 00:00:00
abstract:OBJECTIVE:To systematically determine the impact of growth hormone therapy on adult height of children with idiopathic short stature. DESIGN:Systematic review. DATA SOURCES:Cochrane Central Register of Controlled Trials, Medline, and the bibliographic references from retrieved articles of randomised and non-randomise...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,评审
doi:10.1136/bmj.c7157
更新日期:2011-03-11 00:00:00
abstract:OBJECTIVES:To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences, and costs. DESIGN:Randomised c...
journal_title:BMJ (Clinical research ed.)
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1136/bmj.38558.393669.E0
更新日期:2005-09-03 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.299.6692.163
更新日期:1989-07-15 00:00:00
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journal_title:BMJ (Clinical research ed.)
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更新日期:2003-07-26 00:00:00
abstract:OBJECTIVE:To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN:Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING:Department of neurology, University of Glasgow, Southern General Hospital; depar...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.304.6833.1010
更新日期:1992-04-18 00:00:00
abstract:OBJECTIVE:To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. DESIGN:Cohort study. SETTING:Control programme in Ibba, southern Sudan. PARTICIPANTS:1055 adults and children newly diagnosed with second stage disease in a 16 month period. MAIN OUTCOME MEASU...
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pub_type: 杂志文章
doi:10.1136/bmj.39485.592674.BE
更新日期:2008-03-29 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.314.7073.38
更新日期:1997-01-04 00:00:00
abstract:OBJECTIVE:To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions. DESIGN:Systematic review with meta-analysis. DATA SOURCES:Medline, PsycINFO, Embase, and the Cochrane Central...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,meta分析,评审
doi:10.1136/bmj.g2646
更新日期:2014-05-14 00:00:00
abstract:OBJECTIVES:To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm(3) at start of antiretroviral therapy. DESIGN:Cohort study. SETTING:Outpatient HIV c...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.d6016
更新日期:2011-10-11 00:00:00
abstract:OBJECTIVE:To examine whether the decline in child injury death rates between 1981 and 1991 varied by social class. DESIGN:Comparison of class specific child injury death rates for 1979, 1980, 1982, and 1983, with those for the four years 1989-92. SETTING:England and Wales. SUBJECTS:Children aged 0-15 years. MAIN OU...
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pub_type: 杂志文章
doi:10.1136/bmj.313.7060.784
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.g6572
更新日期:2014-12-02 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/bmj.k3478
更新日期:2018-09-12 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2016-03-02 00:00:00
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doi:10.1136/bmj.308.6928.572
更新日期:1994-02-26 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/bmj.i2868
更新日期:2016-06-15 00:00:00
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doi:10.1136/bmj.297.6654.966
更新日期:1988-10-15 00:00:00
abstract:OBJECTIVE:To compare perinatal outcomes in births of women with versus without a history of bariatric surgery. DESIGN:Population based matched cohort study. SETTING:Swedish national health service. PARTICIPANTS:1,742,702 singleton births identified in the Swedish medical birth register between 1992 and 2009. For eac...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.f6460
更新日期:2013-11-12 00:00:00
abstract:OBJECTIVE:To estimate the high risk group for cardiovascular disease in a well defined Norwegian population according to European guidelines and the systematic coronary risk evaluation system. DESIGN:Modelling study. SETTING:Nord-Tröndelag health study 1995-7 (HUNT 2), Norway. PARTICIPANTS:5548 participants of the N...
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pub_type: 杂志文章
doi:10.1136/bmj.38555.648623.8F
更新日期:2005-09-10 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
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更新日期:2014-07-23 00:00:00
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pub_type: 杂志文章
doi:10.1136/bmj.305.6861.1074
更新日期:1992-10-31 00:00:00
abstract::One hundred and two patients returned structured questionnaires sent to clinics for sickle cell disease in the United Kingdom in order to gain greater insight into the patients' perception of painful crises. Most patients who suffer pain crises experience a prodromal stage that should be investigated further to find o...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.297.6646.452
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abstract:OBJECTIVE:To investigate the relation between total fat intake and body weight in adults and children. DESIGN:Systematic review and meta-analysis of randomised controlled trials and cohort studies. DATA SOURCES:Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials to June 2010. INCLUSION CR...
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pub_type: 杂志文章,meta分析,评审
doi:10.1136/bmj.e7666
更新日期:2012-12-06 00:00:00
abstract:OBJECTIVE:To determine the prevalence of sexually transmitted diseases in patients with normal and abnormal cervical smears. DESIGN:A prospective study of asymptomatic women with normal cervical smears attending their general practitioner and newly referred patients with abnormal smears attending a colposcopy clinic. ...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.302.6768.82
更新日期:1991-01-12 00:00:00