P06 Paternal exposure to methotrexate and the risk of miscarriage – a register based nationwide cohort study

ObjectiveTo study the association between paternal exposure to methotrexate within three month before conception and during the first trimester of pregnancy and the risk of miscarriage.MethodsWe conducted a nationwide cohort study identifying all registered pregnancies in Denmark from 1997 to 2015. All births were identified using the Medical Birth Registry, and all records of induced abortion and miscarriage were from the National Hospital Register. Data on drug use were from the National Prescription Register. Cox proportional hazard regression models were used to calculate the hazard of miscarriage in women with a partner exposed to methotrexate. The study was approved by the Danish Data Protection Agency (2015-41-4309).ResultsWe identified 1,364,063 registered pregnancies with known paternity, of whom 520 fathers were exposure to methotrexate within the three months before conception to the end of the first trimester. Among these, 46 (8.9%) experienced a miscarriage compared to 122,926 (9.0%) among the unexposed.There was no increased risk of experiencing a miscarriage in pregnancies to men exposed to methotrexate before pregnancy compared to unexposed (adjusted hazard ratio 0.99 (CI95% 0.67- 1.46)). Furthermore, we found no increased risk of experiencing a miscarriage in pregnancies to men exposed to methotrexate during first trimester compared to unexposed (adjusted hazard ratio 0.90 (CI95% 0.61–1.32)).ConclusionWe found no association between paternal exposure to methotrexate before and during early pregnancy and miscarriage. Available data suggest that paternal methotrexate exposure should not be of major concern. Multinational recommendations could be changed accordingly.Disclosure(s)Nothing to disclose

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Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

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Maternal and child gluten intake and risk of type 1 diabetes: The Norwegian Mother and Child Cohort Study

10.1101/19001883 ◽

2019 ◽

Author(s):

Nicolai A Lund-Blix ◽

German Tapia ◽

Karl Mårild ◽

Anne Lise Brantsaeter ◽

Pål R Njølstad ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Confidence Interval ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Pregnancy Cohort ◽

Increased Risk ◽

Mother And Child

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.

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The Wuhan Twin Birth Cohort (WTBC)

Twin Research and Human Genetics ◽

10.1017/thg.2017.24 ◽

2017 ◽

Vol 20 (4) ◽

pp. 355-362

Author(s):

Jinzhu Zhao ◽

Shaoping Yang ◽

Anna Peng ◽

Zhengmin Qian ◽

Hong Xian ◽

...

Keyword(s):

Cohort Study ◽

Birth Cohort ◽

Medical Information ◽

First Trimester ◽

Population Based ◽

Health Examination ◽

Birth Registry ◽

Twin Birth ◽

First Trimester Of Pregnancy

The Wuhan Pre/Post-Natal Twin Birth Registry (WPTBR) is one of the largest twin birth registries with comprehensive medical information in China. It recruits women from the first trimester of pregnancy and their twins from birth. From January 2006 to May 2016, the total number of twins enrolled in WPTBR is 13,869 twin pairs (27,553 individuals). The WPTBR initiated the Wuhan Twin Birth Cohort (WTBC). The WTBC is a prospective cohort study carried out through incorporation of three samples. The first one comprises 6,920 twin pairs, and the second one, 6,949 twin pairs. Both are population-based samples linked to the WPTBR and include pre- and post-natal information from WPTBR. The second sample includes neonatal blood spots as well. Using a hospital-based approach, we recently developed a third sample with a target enrolment of 1,000 twin pairs and their mothers. These twins are invited, via their parents, to participate in a periodic health examination from the first trimester of pregnancy to 18 years. Biological samples are collected initially from the mother, including blood, urine, cord blood, cord, amniotic fluid, placenta, breast milk and meconium, and vaginal secretions, and later from the twins, including meconium, stool, urine, and blood. This article describes the design, recruitment, follow-up, data collection, and measures, as well as ongoing and planned analyses at the WTBC. The WTBC offers a unique opportunity to follow women from prenatal to postnatal, as well as follow-up of their twins. This cohort study will expand the understanding of genetic and environmental influences on pregnancy and twins’ development in China.

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The Association Between Attention-Deficit Hyperactivity Disorder, Injuries, and Methylphenidate

Global Pediatric Health ◽

10.1177/2333794x19845920 ◽

2019 ◽

Vol 6 ◽

pp. 2333794X1984592

Author(s):

Sharon Shem-Tov ◽

Gabriel Chodick ◽

Dalia Weitzman ◽

Gideon Koren

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Cohort Study ◽

Attention Deficit ◽

Injury Rate ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Severe Injuries ◽

Traumatic Injuries ◽

Hyperactivity Disorder ◽

Increased Risk

Objective. To evaluate the relationship between attention-deficit hyperactivity disorder (ADHD) and injuries and to verify whether methylphenidate (MPH), is associated with decreasing the risk of injuries. Methods. A retrospective cohort study using the computerized database of Maccabi Healthcare Services. The ADHD cohort included all children between 12 and 20 years of age, newly diagnosed with ADHD between 2003 and 2013. The comparison cohort was composed of children who were not diagnosed with ADHD. The primary outcome was traumatic injuries. A Cox proportional hazard regression analysis was conducted to estimate ADHD effects on the risk of injuries. We also conducted a nested case-control study to examine how MPH influences this relationship. Results. A total of 59 798 children were included in the cohort study; 28 921 were classified as exposed (ADHD cohort) and 30 877 were unexposed. The traumatic injuries incidence in the exposed group was significantly higher (adjusted hazard ratio = 1.63 [95% confidence interval = 1.60-1.66]). Similar increased risk was documented also for severe injuries (adjusted hazard ratio = 1.72 [1.59-1.86]). MPH use was significantly associated with 28% lower injury events. Therapy groups were significantly associated with 29% to 40% lower injuries rate for medium- or long-acting MPH. The intensity of therapy was significantly associated with 29% to 33% lower injury rate when the intensity was lower than 0.69 mg/kg/day. Conclusion. Children with ADHD have a 60% increased odds of experiencing an injury. Treatment with MPH reduced the risk by up to 28%. The individual and financial cost secondary to injuries, underscores the public health significance of this problem. Injury prevention should be considered in clinical evaluation of MPH risks and benefits, beyond the conventional consideration of enhancing academic achievements.

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Dementia and the Risk of Periodontitis: A Population-Based Cohort Study

Journal of Dental Research ◽

10.1177/00220345211037220 ◽

2021 ◽

pp. 002203452110372

Author(s):

K.S. Ma ◽

H. Hasturk ◽

I. Carreras ◽

A. Dedeoglu ◽

J.J. Veeravalli ◽

...

Keyword(s):

Cohort Study ◽

Relative Risk ◽

Propensity Score ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Rank Test ◽

Confounding Factors ◽

Proportional Hazard ◽

Cox Proportional Hazard ◽

Log Rank Test

Dementia and Alzheimer’s disease (AD) are proposed to be comorbid with periodontitis (PD). It is unclear whether PD is associated with dementia and AD independent of confounding factors. We aimed at identifying the relationship between the longitudinal risk of developing PD in a cohort of patients with dementia and AD who did not show any signs of PD at baseline. In this retrospective cohort study, 8,640 patients with dementia without prior PD were recruited, and 8,640 individuals without dementia history were selected as propensity score–matched controls. A Cox proportional hazard model was developed to estimate the risk of developing PD over 10 y. Cumulative probability was derived to assess the time-dependent effect of dementia on PD. Of the 8,640 patients, a sensitivity test was conducted on 606 patients with AD-associated dementia and 606 non-AD propensity score–matched controls to identify the impact of AD-associated dementia on the risk for PD. Subgroup analyses on age stratification were included. Overall 2,670 patients with dementia developed PD. The relative risk of PD in these patients was significantly higher than in the nondementia group (1.825, 95% CI = 1.715 to 1.942). Cox proportional hazard models showed that patients with dementia were more likely to have PD than individuals without dementia (adjusted hazard ratio = 1.915, 95% CI = 1.766 to 2.077, P < 0.0001, log-rank test P < 0.0001). The risk of PD in patients with dementia was age dependent ( P values for all ages <0.0001); younger patients with dementia were more likely to develop PD. The findings persisted for patients with AD: the relative risk (1.531, 95% CI = 1.209 to 1.939) and adjusted hazard ratio (1.667, 95% CI = 1.244 to 2.232; log-rank test P = 0.0004) of PD in patients with AD were significantly higher than the non-AD cohort. Our findings demonstrated that dementia and AD were associated with a higher risk of PD dependent of age and independent of systemic confounding factors.

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Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study

Acta Endocrinologica ◽

10.1530/eje-20-0686 ◽

2021 ◽

Vol 184 (1) ◽

pp. 143-151

Author(s):

Mijin Kim ◽

Bo Hyun Kim ◽

Hyungi Lee ◽

Hyewon Nam ◽

Sojeong Park ◽

...

Keyword(s):

Cohort Study ◽

Thyroid Cancer ◽

Hormone Therapy ◽

Protective Factor ◽

Premenopausal Women ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cancer Development ◽

Surgery Group ◽

Increased Risk

Objective Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. Design A nationwide cohort study Methods Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). Results During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. Conclusions Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

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Association between Cervical Spondylosis and Migraine: A Nationwide Retrospective Cohort Study

10.20944/preprints201802.0056.v1 ◽

2018 ◽

Author(s):

Wang-Sheng Lin ◽

Tung-Fu Huang ◽

Tien-Yow Chuang ◽

Cheng-Li Lin ◽

Chia-Hung Kao

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Cervical Spondylosis ◽

Population Based ◽

Hazard Ratio ◽

Cox Proportional Hazard ◽

Longitudinal Association ◽

Cox Proportional Hazard Regression

Background: Few studies have investigated the longitudinal association between cervical spondylosis (CS) and migraine by using a nationwide population-based database. Methods: We conducted a retrospective cohort study from 2000 to 2011 identifying 27,930 cases of cervical spondylosis and 111,720 control subjects (those without cervical spondylosis) from a single database. The subjects were frequency-matched on the basis of sex, age, and diagnosis date. The non- cervical spondylosis cohort was four times the size of the cervical spondylosis cohort. To quantify the effects of cervical spondylosis on the risk of migraine, univariate and multivariate Cox proportional hazard regression analyses were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: After a 10-year follow-up controlling for potential confounding factors, overall migraine incidence was higher in the cervical spondylosis cohort than in the non- cervical spondylosis cohort (5.16 and 2.09 per 1,000 people per year, respectively; crude hazard ratio = 2.48, 95% confidence interval = 2.28–2.69) with an adjusted hazard ratio of 2.03 (95% confidence interval = 1.86–2.22) after accounting for sex, age, comorbidities, and medication. Individuals with myelopathy in the cervical spondylosis cohort had a 2.19 times (95% confidence interval = 1.80–2.66) higher incidence of migraine compared than did those in the non- cervical spondylosis cohort. Conclusion: Individuals with cervical spondylosis exhibited a higher risk of migraine than those without cervical spondylosis. The migraine incidence rate was even higher among individuals with cervical spondylotic myelopathy.

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The Influence of Constipation on Asthma: A Real-world, Population-based Cohort Study

10.22541/au.161089372.23442799/v1 ◽

2021 ◽

Author(s):

Yen Chu Huang ◽

Meng Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

World Population ◽

Research Database ◽

Cox Regression Analysis ◽

Increased Risk ◽

One Year

Background Among respiratory diseases, asthma is one of the most burdensome disorder worldwide. Growing evidence disclose gut dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microflora. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess the risk of asthma in constipated patients by a nationwide population-based cohort study. Methods We analyzed 82421 constipated patients and 82421 individuals without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Analysis of propensity score was utilized to match age, gender, comorbidities, and medications at a ratio of 1:1. Besides, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were conducted. Results The incidence of asthma was 10.8 per 1,000 person-years in the constipation group, which was higher than the rate of 5.6 per 1,000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, and medications, constipated patients had a 1.91-fold greater risk of asthma compared to those without constipation (adjusted hazard ratio [aHR]: 1.91 (95% C.I. 1.84-1.99). In subgroup analyses, patients aged 20-39 years had a 2.04-fold highest risk of asthma in the constipation cohort (aHR:2.04, 95% CI, 1.84-2.26). Besides, the severity of constipation is associated with an increased risk of asthma; the aHR was 1.76 (1.69-1.85), 2.15(2.03-2.27), and 2.29(2.10-2.49) for < 3 times, 3-12 times, and ≥12 times of laxatives prescription within one year, respectively. (p<0.001) Moreover, constipated patients had a higher likelihood of asthma, regardless of gender, comorbidities, and medications. Conclusion Constipation relates to a significantly increased risk of asthma. Physicians should be aware of the possibility of asthma in constipated people. Further research is warranted to investigate the possible pathological mechanisms of this association.

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SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study

BMJ ◽

10.1136/bmj-2021-068665 ◽

2021 ◽

pp. e068665

Author(s):

Anders Husby ◽

Jørgen Vinsløv Hansen ◽

Emil Fosbøl ◽

Emilia Myrup Thiesson ◽

Morten Madsen ◽

...

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Absolute Rate ◽

Hazard Ratios ◽

Increased Risk ◽

The Absolute

AbstractObjectiveTo investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis.DesignPopulation based cohort study.SettingDenmark.Participants4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021.Main outcome measuresThe primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders.ResultsDuring follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination.ConclusionsVaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

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Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study

Epidemiology and Infection ◽

10.1017/s0950268812002178 ◽

2012 ◽

Vol 141 (8) ◽

pp. 1749-1755 ◽

Cited By ~ 13

Author(s):

J. T. ANDERSEN ◽

M. PETERSEN ◽

E. JIMENEZ-SOLEM ◽

K. BROEDBAEK ◽

E. W. ANDERSEN ◽

...

Keyword(s):

Regression Analysis ◽

Cohort Study ◽

Folic Acid ◽

First Trimester ◽

Induced Abortion ◽

Time Dependent ◽

Proportional Hazard ◽

Acid Cycle ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Regression

SUMMARYThe antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2·04 (95% confidence interval 1·43–2·91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

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