scholarly journals Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study

BMJ ◽  
2020 ◽  
pp. m331 ◽  
Author(s):  
Heng Fan ◽  
Ruth Gilbert ◽  
Finbar O’Callaghan ◽  
Leah Li
Keyword(s):  
First Trimester ◽  
Population Based ◽  
Autism Spectrum ◽  
Macrolide Antibiotics ◽  
Study Cohort ◽  
Major Malformation ◽  
Cardiovascular Malformations ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
The Uk

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

scholarly journals Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings

2018 ◽  
Vol 49 (1) ◽  
pp. 84-91 ◽  
Author(s):  
Elina Jokiranta-Olkoniemi ◽  
Keely Cheslack-Postava ◽  
Petteri Joelsson ◽  
Auli Suominen ◽  
Alan S. Brown ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Population Based ◽  
Autism Spectrum ◽  
Schizophrenia Spectrum Disorders ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Spectrum Disorders

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

Obstetric oxytocin exposure and ADHD and ASD among Danish and Finnish children

2020 ◽  
Author(s):  
Lonny Stokholm ◽  
Mette Juhl ◽  
Nicole M Talge ◽  
Mika Gissler ◽  
Carsten Obel ◽  
...  
Keyword(s):  
Population Based ◽  
Autism Spectrum ◽  
Labour Induction ◽  
Prenatally Exposed ◽  
Hyperactivity Disorder ◽  
Diagnostic Codes ◽  
Increased Risk ◽  
Specific Association ◽  
And Gender ◽  
Confounder Adjustment

Abstract Background Some studies have indicated an increased risk of attention deficit hyperactivity disorder (ADHD) and a small, sex-specific association with autism spectrum disorder (ASD) among children prenatally exposed to obstetric oxytocin. Since oxytocin is widely used in the obstetric ward, these potentially deleterious effects are of concern. Thus, we aimed to examine whether obstetric oxytocin treatment for labour induction or augmentation is associated with ADHD and ASD in offspring born in a two-country design based on data from Denmark and Finland. Methods This population-based study used data from national registers in Denmark and Finland. Singletons born in Denmark 2000–10 (n = 577 380) and Finland 1991–2010 (n = 945 543), who survived infancy, were followed until 31 December 2015. ADHD and ASD were defined using diagnostic codes. For ADHD, we also included information on prescribed and redeemed ADHD medication in the definition. Hazards ratios (HRs) with 95% confidence intervals (CI), modelled with age as the underlying time scale, were calculated to estimate the associations. Results Oxytocin was used in 31% and 46% of the included deliveries in Denmark and Finland, respectively. In crude analyses, prenatal oxytocin was associated with an approximately 20% increased risk of ADHD and ASD, but confounder adjustment attenuated the association. The adjusted HR was 1.03, 95% CI 1.01–1.05, for ADHD and 1.05, 95% CI 1.02–1.08, for ASD. The results were similar in across country and gender. Conclusions We found an association between synthetic oxytocin and ADHD or ASD which is unlikely to reflect a causal association and thus should not support the concern of clinical use. Our results help to allay concerns of obstetric use of oxytocin causing ADHD or ASD.

scholarly journals Association of Attention deficit hyperactivity disorder and Kawasaki disease: a nationwide population-based cohort study

2015 ◽  
Vol 25 (6) ◽  
pp. 573-580 ◽  
Author(s):  
H.-C. Kuo ◽  
W.-C. Chang ◽  
L.-J. Wang ◽  
S.-C. Li ◽  
W.-P. Chang
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Kawasaki Disease ◽  
Attention Deficit ◽  
Survival Rates ◽  
Population Based ◽  
Study Cohort ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Comparison Cohort ◽  
Cox Proportional Hazard Regression

Aims.The association between Kawasaki disease (KD) and Attention deficit hyperactivity disorder (ADHD) has rarely been studied. In this study, we investigated the hypothesis that KD may increase the risk of ADHD using a nationwide Taiwanese population-based claims database.Methods.Our study cohort consisted of patients who were diagnosed with KD between January 1997 and December 2005 (N = 651). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 3255). The cumulative incidence of ADHD was 3.89/1000 (from 0.05 to 0.85) in this study. All subjects were tracked for 5 years from the date of cohort entry to identify whether or not they had developed ADHD. Cox proportional hazard regression analysis was performed to evaluate 5-year ADHD-free survival rates.Results.Of all patients, 83 (2.1%) developed ADHD during the 5-year follow-up period, of whom 21 (3.2%) had KD and 62 (1.9%) were in the comparison cohort. The patients with KD seemed to be at an increased risk of developing ADHD (crude hazard ratio (HR): 1.71; 95% confidence interval (CI) = 1.04–2.80; p < 0.05). However, after adjusting for gender, age, asthma, allergic rhinitis, atopic dermatitis and meningitis, the adjusted hazard ratios (AHR) of the ADHD in patients with KD showed no association with the controls (AHR: 1.59; 95% CI = 0.96–2.62; p = 0.07). We also investigated whether or not KD was a gender-dependent risk factor for ADHD, and found that male patients with KD did not have an increased risk of ADHD (AHR: 1.62; 95% CI = 0.96–2.74; p = 0.07) compared with the female patients.Conclusions.The findings of this population-based study suggest that patients with KD may not have an increased risk of ADHD and whether or not there is an association between KD and ADHD remains uncertain.

Paternal exposure to antiepileptic drugs and offspring outcomes: a nationwide population-based cohort study in Sweden

2020 ◽  
Vol 91 (9) ◽  
pp. 907-913
Author(s):  
Torbjörn Tomson ◽  
Giulia Muraca ◽  
Neda Razaz
Keyword(s):  
Intellectual Disability ◽  
Antiepileptic Drugs ◽  
Congenital Malformations ◽  
Population Based ◽  
Autism Spectrum ◽  
Adverse Outcomes ◽  
Neurodevelopmental Outcomes ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
Major Congenital Malformations

ObjectivesTo investigate the association between paternal use of antiepileptic drugs (AEDs) and adverse neurodevelopmental outcomes and major congenital malformations (MCM) in the offspring.MethodsUsing nationwide Swedish registries, we included 1 144 795 births to 741 726 fathers without epilepsy and 4544 births to 2955 fathers with epilepsy. Of these, 2087 (45.9%) were born to fathers with epilepsy who had dispensed an AED during the conception period. Children who had both parents with epilepsy were excluded. The incidence rate of MCM, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and intellectual disability in offspring was analysed.ResultsOffspring of fathers exposed to AEDs did not show an increased risk of MCM (adjusted OR 0.9, 95% CI 0.7 to 1.2), autism (adjusted HR (aHR) 0.9, 95% CI 0.5 to 1.7), ADHD (aHR 1.1, 95% CI 0.7 to 1.9) or intellectual disability (aHR 1.3, 95% CI 0.6 to 2.8) compared with offspring of fathers with epilepsy not exposed to AEDs. Among offspring of fathers with epilepsy who used valproate in monotherapy during conception, rates of autism (2.9/1000 child-years) and intellectual disability (1.4/1000 child-years) were slightly higher compared with the offspring of fathers with epilepsy who did not use AEDs during conception (2.1/1000 child-years autism, 0.9/1000 child-years intellectual disability), but in the propensity-score adjusted analyses, no statistically significant increased risk of adverse outcomes was found.ConclusionsPaternal AED use during conception is not associated with adverse outcomes in the offspring.

scholarly journals Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2254
Author(s):  
Matteo Franchi ◽  
Roberta Tritto ◽  
Luigi Tarantini ◽  
Alessandro Navazio ◽  
Giovanni Corrao
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Adjuvant Therapy ◽  
Large Population ◽  
Positive Association ◽  
Population Based ◽  
Study Cohort ◽  
Increased Risk ◽  
Post Menopausal ◽  
New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

scholarly journals What families in the UK use to manage attention-deficit/hyperactivity disorder (ADHD): a survey of resource use

2020 ◽  
Vol 4 (1) ◽  
pp. e000771
Author(s):  
Philippa Fibert ◽  
Clare Relton
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Support Groups ◽  
Attention Deficit ◽  
Service Use ◽  
Behavioural Change ◽  
Behavioural Therapy ◽  
Autism Spectrum ◽  
Convenience Sample ◽  
Hyperactivity Disorder ◽  
The Uk

ObjectiveTo identify interventions being used to manage attention-deficit/hyperactivity disorder (ADHD) in the UK.DesignA survey within the Sheffield Treatments for ADHD Research project. A convenience sample of participants in the UK who consented to join an observational cohort were asked closed questions about medication, behavioural change programmes and service use, and an open-ended question about what else they used.SettingA broad variety of non-National Health Service, non-treatment seeking settings throughout the UK, including local authority organisations, schools, ADHD and autism spectrum condition support groups and social media.ParticipantsFamilies of children aged 5–18 with carer reported ADHD and Conners Global Index (CGI) T scores of 55+.ResultsResponses from 175 families were analysed. The mean age of the children was 10.21 (2.44), and two-thirds (n=114) had additional diagnoses. The majority used medications to manage ADHD (n=120) and had participated in a parenting class (n=130). Just over a quarter (28%, n=49) did not use ADHD medications, and used sleep medications. Just under half had consulted psychologists (n=83), and 32 had participated in other talking therapies such as psychotherapy, counselling and cognitive–behavioural therapy. A few used aids such as reward charts or fiddle toys (n=17) and participated in activities (mostly physical) (n=14). A substantial minority (78/175) had used non-mainstream treatments, the most popular being homoeopathy (n=32), nutritional interventions (n=21) and bodywork such as massage or cranial osteopathy (n=9).ConclusionsFamilies reported use of a wide variety of treatments to help with management of their children with ADHD in addition to their use of mainstream treatments.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

2018 ◽  
Vol 49 (14) ◽  
pp. 2397-2404 ◽  
Author(s):  
Mu-Hong Chen ◽  
Ju-Wei Hsu ◽  
Kei-Lin Huang ◽  
Tung-Ping Su ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Population Based ◽  
Autism Spectrum ◽  
The Public ◽  
First Degree Relatives ◽  
Relative Risks ◽  
Dependent Relationship ◽  
Increased Risk ◽  
Bipolar Patients

AbstractBackgroundBipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.MethodsAmong the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.ResultsFDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.ConclusionsOur study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

scholarly journals Maternal spontaneous abortion and the risk of attention-deficit/hyperactivity disorder in offspring: a population-based cohort study

2020 ◽  
Vol 35 (5) ◽  
pp. 1211-1221 ◽  
Author(s):  
Hui Wang ◽  
Fei Li ◽  
Maohua Miao ◽  
Yongfu Yu ◽  
Honglei Ji ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Spontaneous Abortion ◽  
Attention Deficit ◽  
Development Program ◽  
Population Based ◽  
Parental History ◽  
Maternal History ◽  
Hyperactivity Disorder ◽  
Increased Risk ◽  
History Of

Abstract STUDY QUESTION Is a maternal history of spontaneous abortion (SA) associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring? SUMMARY ANSWER Our results suggest an association between maternal history of SA and ADHD in offspring, with the risk increasing with the number of maternal SA and highest in the firstborn children whose mothers had had recurrent SAs after adjusting for a number of potential confounders. WHAT IS KNOWN ALREADY A history of SA has been associated with more complications in next pregnancies and adverse childbirth outcomes, which are risk factors for ADHD in the offspring. However, no previous study has investigated whether maternal SA increases risk of ADHD in the offspring. STUDY DESIGN, SIZE, DURATION This population-based study included all live-born children in Denmark from 1 January 1995 to 31 December 2012 (n = 1 062 667). All children were followed from 3 years of age until the day of ADHD diagnosis, death, emigration or 31 December 2016, whichever came first. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 130 206 (12.2%) children born to mothers who had at least one SA. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN RESULTS AND THE ROLE OF CHANCE During a median follow-up of 9.4 years (interquartile range, 5.4–14.3), 25 747 children were diagnosed with ADHD. Overall, children of mothers with a history of SA had an increased rate of ADHD (HR, 1.11; 95% CI, 1.07 to 1.15). The HRs increased with the number of maternal SA, 1.09 (95% CI, 1.05 to 1.13) for one SA and 1.22 (95% CI, 1.12 to 1.33) for at least two SAs, respectively. These findings were consistent when we took into consideration a number of factors, such as maternal socioeconomic status, type of SA, birth order, parental history of psychiatric disorders, pregnancy characteristics and adverse birth outcomes. LIMITATIONS, REASONS FOR CAUTION Misclassification of SA was possible as we used population-based register data to capture maternal history of SA. However, any misclassification of maternal history of SA would be non-differential with regard to the diagnosis of ADHD in offspring, which generally leads to underestimation of the associations. Furthermore, probabilistic sensitivity analysis suggested that only 1% of change in the estimate may have been due to misclassification of SA. WIDER IMPLICATIONS OF THE FINDINGS SA is quite frequent (varying from 15 to 20%), and a small increase of neurodevelopmental problems in offspring could have major public health implications. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (No. 81703237, No. 81530086 and No. 81761128035), National Key Research and Development Program (2018YFC1002801, 2016YFC1000505), Shanghai Municipal Commission of Health and Family Planning (No. 2017ZZ02026, No. 2017EKHWYX-02), the Novo Nordisk Foundation (NNF18OC0052029), the Danish Council for Independent Research (DFF-6110-00019), the Nordic Cancer Union (176673, 186200 and R217-A13234-18-S65), Karen Elise Jensens Fond (2016) and Xinhua Hospital of Shanghai Jiao Tong University School of Medicine (2018YJRC03). All authors report no conflict of interest. TRIAL REGISTRATION NUMBER NA.

scholarly journals Severity of COVID-19 in children with cancer: Report from the United Kingdom Paediatric Coronavirus Cancer Monitoring Project

2020 ◽  
Author(s):  
Gerard C. Millen ◽  
Roland Arnold ◽  
Jean-Baptiste Cazier ◽  
Helen Curley ◽  
Richard G. Feltbower ◽  
...  
Keyword(s):  
Severe Infection ◽  
Paediatric Population ◽  
Population Based ◽  
Children With Cancer ◽  
The United Kingdom ◽  
Increased Risk ◽  
Polymerase Chain ◽  
The Uk ◽  
Active Care ◽  
Care Support

Abstract Background Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK. Methods Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital. Results Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%. Conclusions Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.

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