Maternal antibiotic use during pregnancy and asthma in children: population-based cohort study and sibling design

Antibiotic use during pregnancy may affect asthma risk in offspring. However, epidemiological studies yielded conflicting findings, with an observed association possibly confounded by shared familial factors. We sought to assess the association between maternal antibiotic use during pregnancy and childhood asthma in the offspring, by accounting for time-stable familial factors.We conducted a population-based cohort study and sibling study using data from Danish nationwide registers, which comprised 407 804 liveborn singletons from 2005 to 2011. Antibiotic use during pregnancy was defined as at least one antibiotic prescription filled by the mother from 1 month prior to pregnancy up until delivery, identified in the National Prescription Registry. First-time asthma in the offspring was determined by hospital treatment or asthma medication treatment after age 5 years. We estimated hazard ratios (HRs) of asthma using Cox regression in the population-based cohort and stratified Cox regression in the sibling cohort.Approximately 36.5% of pregnant women redeemed antibiotic prescriptions. Antibiotic use during pregnancy was associated with childhood asthma in cohort analyses (HR 1.21, 95% CI 1.18–1.24), but not in sibling analyses (HR 0.96, 95% CI 0.90–1.03). In the population-based analyses, higher risks of asthma were seen with longer duration of maternal antibiotic use, a higher number of prescriptions and prescriptions of multiple types of antibiotics. All these associations disappeared in the sibling analyses.The associations observed by previous studies for prenatal exposure to antibiotics and offspring asthma risk are likely to be due to confounding factors shared within families.

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Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison

Molecular Psychiatry ◽

10.1038/s41380-021-01406-5 ◽

2022 ◽

Author(s):

Yuchen Li ◽

Arvid Sjölander ◽

Huan Song ◽

Sven Cnattingius ◽

Fang Fang ◽

...

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Analysis ◽

Epidemiological Studies ◽

Population Based ◽

Paternal Age ◽

Perinatal Factors ◽

Sibling Comparison ◽

Familial Environment ◽

Subsequent Risk

AbstractLittle is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973–2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32–36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.12] and sibling analyses (HR 1.10, 95% CI 1.02–1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

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Dose, Timing, and Spectrum of Prenatal Antibiotic Exposure and Risk of Childhood Asthma

Clinical Infectious Diseases ◽

10.1093/cid/ciaa085 ◽

2020 ◽

Author(s):

Kedir N Turi ◽

Tebeb Gebretsadik ◽

Tan Ding ◽

Andrew Abreo ◽

Cosby Stone ◽

...

Keyword(s):

Pregnant Women ◽

Broad Spectrum ◽

Childhood Asthma ◽

Antibiotic Use ◽

Population Based ◽

Antibiotic Exposure ◽

Logistic Regression Models ◽

Asthma Risk ◽

Timing Of Exposure ◽

Important Evidence

Abstract Background The potential for prenatal antibiotic exposure to influence asthma risk is not clear. We aimed to determine the effect of timing, dose, and spectrum of prenatal antibiotic exposure on the risk of childhood asthma. Methods We conducted a population-based cohort study of 84 214 mother–child dyads to examine the association of prenatal antibiotic exposure and childhood asthma using multivariable logistic regression models. Results Sixty-four percent of pregnant women received antibiotics. Prenatal antibiotic exposure was associated dose-dependently with increased odds of childhood asthma (adjusted odds ratio [aOR] for interquartile increase of 2 courses [interquartile range, 0–2], 1.26 [95% confidence interval {CI}, 1.20–1.33]). Among children exposed to at least 1 course in utero, the effect of timing at the first course was moderated by total maternal courses. Among pregnant women receiving a single antibiotic course, timing of exposure had no effect on childhood asthma risk. Among women receiving > 1 course, early exposure of the first course was associated with greater childhood asthma risk. Compared to narrow spectrum–only antibiotic use, broad spectrum–only antibiotic exposure was associated with increased odds of asthma (aOR, 1.14 [95% CI, 1.05–1.24]). There were effect modifications (P < .001) by maternal asthma on total courses, and on timing of the first course, significant only among those without maternal asthma. Conclusions Increased cumulative dose, early pregnancy first course, and broad-spectrum antibiotic exposure were associated with childhood asthma risk. Our study provides important evidence supporting judicious prenatal antibiotic use, particularly timing of use and choice of antibiotics, in preventing subsequent childhood asthma.

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Prenatal antibiotic exposure and childhood asthma: a population-based study

European Respiratory Journal ◽

10.1183/13993003.02070-2017 ◽

2018 ◽

Vol 52 (1) ◽

pp. 1702070 ◽

Cited By ~ 28

Author(s):

Keely Loewen ◽

Barret Monchka ◽

Salaheddin M. Mahmud ◽

Geert 't Jong ◽

Meghan B. Azad

Keyword(s):

Childhood Asthma ◽

Cox Regression ◽

Antibiotic Use ◽

Population Based ◽

Sensitivity Analyses ◽

Antibiotic Exposure ◽

Physician Billing ◽

Increased Risk ◽

Before And After ◽

The Impact

Antibiotic use during infancy alters gut microbiota and immune development and is associated with an increased risk of childhood asthma. The impact of prenatal antibiotic exposure is unclear. We sought to characterise the association between prenatal antibiotic exposure and childhood asthma.We performed a population-based cohort study using prescription records, hospitalisation records and physician billing claims from 213 661 mother–child dyads born in Manitoba, Canada between 1996 and 2012. Associations were determined using Cox regression, adjusting for maternal asthma, postnatal antibiotics and other potential confounders. Sensitivity analyses evaluated maternal antibiotic use before and after pregnancy.36.8% of children were exposed prenatally to antibiotics and 10.1% developed asthma. Prenatal antibiotic exposure was associated with an increased risk of asthma (adjusted hazard ratio (aHR) 1.23, 95% CI 1.20–1.27). There was an apparent dose response (aHR 1.15, 95% CI 1.11–1.18 for one course; aHR 1.26, 95% CI 1.21–1.32 for two courses; and aHR 1.51, 95% CI 1.44–1.59 for three or more courses). Maternal antibiotic use during 9 months before pregnancy (aHR 1.27, 95% CI 1.24–1.31) and 9 months postpartum (aHR 1.32, 95% CI 1.28–1.36) were similarly associated with asthma.Prenatal antibiotic exposure was associated with a dose-dependent increase in asthma risk. However, similar associations were observed for maternal antibiotic use before and after pregnancy, suggesting the association is either not directly causal, or not specific to pregnancy.

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Risk of Aortic Aneurysm and Dissection in Patients with Tuberculosis: A Nationwide Population-Based Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182111075 ◽

2021 ◽

Vol 18 (21) ◽

pp. 11075

Author(s):

Ming-Tsung Chen ◽

Chi-Hsiang Chung ◽

Hung-Yen Ke ◽

Chung-Kan Peng ◽

Wu-Chien Chien ◽

...

Keyword(s):

Cohort Study ◽

Aortic Aneurysm ◽

Cox Regression ◽

Subsequent Development ◽

Population Based ◽

Chronic Inflammatory Disease ◽

Cox Regression Analysis ◽

Aortic Aneurysm And Dissection ◽

Taiwan National Health Insurance ◽

Using Data

Tuberculosis (TB) can cause chronic inflammation. The occurrence of aortic aneurysm (AA) and aortic dissection (AD) may be associated with chronic inflammatory disease, but whether TB increases the risk of AA and AD remains to be determined. This study aimed to investigate the association between TB and the development of AA and AD. We conducted a population-based cohort study using data obtained from the Taiwan National Health Insurance Database. We selected 31,220 individuals with TB and 62,440 individuals without TB by matching the cohorts according to age, sex, and index year at a ratio of 1:2. Cox regression analysis revealed that the TB cohort had a 1.711-fold higher risk of AA and AD than the non-TB cohort after adjustment for sex, age, socioeconomic status, and comorbidities (adjusted hazard ratio = 1.711; 95% confidence interval = 1.098–2.666). Patients with pulmonary, extrapulmonary, and miliary TB had a 1.561-, 1.892-, and 8.334-fold higher risk of AA and AD, respectively. Furthermore, patients with TB at <6 months, 6–12 months, and 1–5 years of follow-up had a 6.896-, 2.671-, and 2.371-fold risk of AA and AD, respectively. Physicians should consider the subsequent development of AA and AD while treating patients with TB.

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Sibling Alcohol Use Disorder Is Associated With Increased Risk for Suicide Attempt

Clinical Psychological Science ◽

10.1177/21677026211025041 ◽

2021 ◽

pp. 216770262110250

Author(s):

Mallory E. Stephenson ◽

Sara Larsson Lönn ◽

Jessica E. Salvatore ◽

Jan Sundquist ◽

Kenneth S. Kendler ◽

...

Keyword(s):

Alcohol Use ◽

Suicide Attempt ◽

Alcohol Use Disorder ◽

Cox Regression ◽

Population Based ◽

Swedish Population ◽

Sibling Pairs ◽

Increased Risk ◽

Using Data ◽

Shared Genetic

The association between having a sibling diagnosed with alcohol use disorder (AUD) and risk for suicide attempt may be attributable to shared genetic liability between AUD and suicidal behavior, effects of environmental exposure to a sibling’s AUD, or both. To distinguish between these alternatives, we conducted a series of Cox regression models using data derived from Swedish population-based registers with national coverage. Among full sibling pairs (656,807 males and 607,096 females), we found that, even after we accounted for the proband’s AUD status, the proband’s risk for suicide attempt was significantly elevated when the proband’s sibling was affected by AUD. Furthermore, the proband’s risk for suicide attempt was consistently higher when the sibling’s AUD registration had occurred more recently. Our findings provide evidence for exposure to sibling AUD as an environmental risk factor for suicide attempt and suggest that clinical outreach may be warranted following a sibling’s diagnosis with AUD.

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Metformin use and long-term risk of benign prostatic hyperplasia: a population-based cohort study

BMJ Open ◽

10.1136/bmjopen-2020-041875 ◽

2020 ◽

Vol 10 (12) ◽

pp. e041875

Author(s):

Mette Nørgaard ◽

Bianka Darvalics ◽

Reimar Wernich Thomsen

Keyword(s):

Cohort Study ◽

Benign Prostatic Hyperplasia ◽

Cox Regression ◽

Population Based ◽

Prostatic Hyperplasia ◽

Haemoglobin A1c ◽

First Line ◽

Intention To Treat ◽

Lowering Drug

ObjectiveTo assess whether metformin use affects risk of benign prostatic hyperplasia (BPH) by comparing the risk of BPH in men with type 2 diabetes who initiated first-line treatment with either metformin or sulfonylurea monotherapy between 2000 or 2006 in Northern Denmark. In this period, sulfonylurea and metformin were both frequently used as first-line glucose-lowering drug (GLD) treatment.DesignA population-based cohort study.SettingNorthern Denmark.ParticipantsAll men who filled at least two prescriptions for metformin or for sulfonylurea, respectively, during their first 6 months of GLD treatment. Follow-up started 6 months after treatment start.Primary outcome measuresRates of subsequent BPH, identified based on community prescriptions for BPH-related treatment or hospital BPH diagnoses, and rates of transurethral resection of the prostate (TURP). Rates in metformin and sulfonylurea users were compared overall and stratified by 6-month haemoglobin A1c (HbA1c) using Cox regression and an intention-to-treat (ITT) approach and an as-treated analysis.ResultsDuring follow-up, less than five persons were lost to follow-up due to emigration. In 3953 metformin initiators with a median follow-up of 10 years, the 10-year cumulative BPH incidence was 25.7% (95% CI 24.2 to 27.1). Compared with 5958 sulfonylurea users (median follow-up 8 years, 10-year cumulative incidence 27.4% (95% CI 26.2 to 28.6)), the crude HR for BPH was 0.83 (95% CI 0.77 to 0.89) and adjusted HR in the ITT analyses was 0.97 (95% CI 0.88 to 1.06). For TURP, the adjusted HR was 0.96 (95% CI 0.63 to 1.46). In the as-treated analysis, adjusted HR for BPH was 0.91 (95% CI 0.81 to 1.02).ConclusionsCompared with sulfonylurea, metformin did not substantially reduce the incidence of BPH in men with diabetes.

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Effect of introducing human papillomavirus genotyping into real-world screening on cervical cancer screening in China: a retrospective population-based cohort study

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211010939 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110109

Author(s):

Binhua Dong ◽

Huachun Zou ◽

Xiaodan Mao ◽

Yingying Su ◽

Hangjing Gao ◽

...

Keyword(s):

Cervical Cancer ◽

Cohort Study ◽

Human Papillomavirus ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Cox Regression ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Hpv Genotyping ◽

Cytology Screening

Background: China’s Fujian Cervical Pilot Project (FCPP) transitioned cervical cancer screening from high-risk human papillomavirus (HR-HPV) nongenotyping to genotyping. We investigated the clinical impact of this introduction, comparing performance indicators between HR-HPV genotyping combined with cytology screening (HR-HPV genotyping period) and the previous HR-HPV nongenotyping combined with cytology screening (HR-HPV nongenotyping period). Methods: A retrospective population-based cohort study was performed using data from the FCPP for China. We obtained data for the HR-HPV nongenotyping period from 1 January 2012 to 31 December 2013, and for the HR-HPV genotyping period from 1 January 2014 to 31 December 2016. Propensity score matching was used to match women from the two periods. Multivariable Cox regression was used to assess factors associated with cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). The primary outcome was the incidence of CIN2+ in women aged ⩾25 years. Performance was assessed and included consistency, reach, effectiveness, adoption, implementation and cost. Results: Compared with HR-HPV nongenotyping period, in the HR-HPV genotyping period, more CIN2+ cases were identified at the initial screening (3.06% versus 2.32%; p < 0.001); the rate of colposcopy referral was higher (10.87% versus 6.64%; p < 0.001); and the hazard ratio of CIN2+ diagnosis was 1.64 (95% confidence interval, 1.43–1.88; p < 0.001) after controlling for health insurance status and age. The total costs of the first round of screening (US$66,609 versus US$65,226; p = 0.293) were similar during the two periods. Higher screening coverage (25.95% versus 25.19%; p = 0.007), higher compliance with age recommendations (92.70% versus 91.69%; p = 0.001), lower over-screening (4.92% versus 10.15%; p < 0.001), and reduced unqualified samples (cytology: 1.48% versus 1.73%, p = 0.099; HR-HPV: 0.57% versus 1.34%, p < 0.001) were observed in the HR-HPV genotyping period. Conclusions: Introduction of an HR-HPV genotyping assay in China could detect more CIN2+ lesions at earlier stages and improve programmatic indicators. Evidence suggests that the introduction of HR-HPV genotyping is likely to accelerate the elimination of cervical cancer in China.

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Gender- and age-related differences of statin use on incident dementia in patients with rheumatoid arthritis: a Nationwide population-based cohort study

Lipids in Health and Disease ◽

10.1186/s12944-021-01465-1 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Tsung-Kun Lin ◽

Jing-Yang Huang ◽

Lung-Fa Pan ◽

Gwo-Ping Jong

Keyword(s):

Rheumatoid Arthritis ◽

Cohort Study ◽

Subgroup Analysis ◽

Cox Regression ◽

Population Based ◽

Age Related ◽

Hazard Ratios ◽

Incident Dementia ◽

Gender And Age ◽

New Onset

Abstract Background Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA. Methods We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted. Results Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients. Conclusion No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40–60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.

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Association between glaucoma surgery and all-cause and cause-specific mortality among elderly patients with glaucoma: a nationwide population-based cohort study

Scientific Reports ◽

10.1038/s41598-021-96063-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Yeop Lee ◽

Hun Lee ◽

Ji Sung Lee ◽

Sol Ah Han ◽

Yoon Jeon Kim ◽

...

Keyword(s):

Cohort Study ◽

Elderly Patients ◽

Cox Regression ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Population Based ◽

Angle Closure ◽

Charlson Comorbidity Index Score ◽

All Cause Mortality ◽

Specific Mortality

AbstractThis population-based, retrospective cohort study aimed to evaluate the association between glaucoma surgery and all-cause and cause-specific mortality among Korean elderly patients with glaucoma. A total of 16210 elderly patients (aged ≥ 60 years) diagnosed with glaucoma between 2003 and 2012 were included, and their insurance data were analyzed. The participants were categorized into a glaucoma surgery cohort (n = 487), which included individuals who had diagnostic codes for open angle glaucoma (OAG) or angle closure glaucoma (ACG) and codes for glaucoma surgery, and a glaucoma diagnosis cohort (n = 15,723), which included patients who had codes for OAG and ACG but not for glaucoma surgery. Sociodemographic factors, Charlson Comorbidity Index score, and ocular comorbidities were included as covariates. Cox regression models were used to assess the association between glaucoma surgery and mortality. The incidence of all-cause mortality was 34.76/1,000 person-years and 27.88/1,000 person-years in the glaucoma surgery and diagnosis groups, respectively. The adjusted hazard ratio (HR) for all-cause mortality associated with glaucoma surgery was 1.31 (95% confidence interval [CI], 1.05–1.62, P = 0.014). The adjusted HR for mortality due to a neurologic cause was significant (HR = 2.66, 95% CI 1.18–6.00, P = 0.018). The adjusted HRs for mortality due to cancer (HR = 2.03, 95% CI 1.07–3.83, P = 0.029) and accident or trauma (HR = 4.00, 95% CI 1.55–10.34, P = 0.004) associated with glaucoma surgery for ACG were significant as well. Glaucoma surgery was associated with an increase of mortality in elderly patients with glaucoma. In particular, the risk of mortality associated with glaucoma surgery due to neurologic causes was significant.

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