Risk of Psychiatric Disorders following Polycystic Ovary Syndrome: A Nationwide Population-Based Cohort Study

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. A higher prevalence of psychiatric comorbidities, including depressive disorder, anxiety disorder, and bipolar disorder has been proved in patients with PCOS. However, a clear temporal causal relationship between PCOS and psychiatric disorders has not been well established.

Objective

We explored the relationship between PCOS and the subsequent development of psychiatric disorders including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder.

Methods

We identified patients who were diagnosed with PCOS by an obstetrician-gynecologist in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without PCOS who were matched according to age and sex. The occurrence of subsequent new-onset psychiatric disorders was evaluated in both cohorts based on diagnoses made by psychiatrists.

Results

The PCOS cohort consisted of 5431 patients, and the comparison cohort consisted of 21,724 matched control patients without PCOS. The incidence of depressive disorder (hazard ratio [HR] 1.296, 95% confidence interval [CI] 1.084–.550), anxiety disorder (HR 1.392, 95% CI 1.121–1.729), and sleep disorder (HR 1.495, 95% CI 1.176–1.899) were higher among the PCOS patients than among the patients in the comparison cohort. In addition, a higher incidence of newly diagnosed depressive disorder, anxiety disorder, and sleep disorder remained significantly increased in all of the stratified follow-up durations (0–1, 1–5, ≥5 y).

Conclusions

PCOS might increase the risk of subsequent newly diagnosed depressive disorder, anxiety disorder, and sleep disorder. The risk of newly diagnosed bipolar disorder, which has often been reported in the literature to be comorbid with PCOS, was not significantly elevated.     

Premicroalbuminuria in Women with Polycystic Ovary Syndrome: A Metabolic Risk Marker

ObjectiveTo determine the relationship between urinary albumin excretion and features of the metabolic syndrome in women with polycystic ovary syndrome (PCOS).MethodsWe retrospectively analyzed the medical records of 189 premenopausal women (mean age ± SD, 28.9 ± 7.7 years) with PCOS and 81 control patients (mean age ± SD, 37.9 ± 8.6 years) from a single endocrinology practice. Exclusion criteria were diabetes, heart disease, kidney disease, use of lipid-lowering agents, and use of antihypertensive agents (except spironolactone). The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. Premicroalbuminuria was defined as an ACR > 7 mg/g.ResultsThe prevalence of ACR > 7 mg/g was 31.2% in the PCOS group (N = 189) and 35.8% in the control group (N = 81). The metabolic syndrome was noted in 16.3% (27 of 166) of patients with PCOS and in 2.9% (2 of 69) of control subjects. Nine percent of patients with PCOS who had an ACR ≤ 7 mg/g but 30.9% of those with an ACR > 7 mg/g had the metabolic syndrome. Patients with PCOS who had an ACR > 7 mg/g had significantly higher blood pressure and alanine aminotransferase levels than did those with an ACR ≤ 7 mg/g. In the patients with PCOS who had an ACR ≤ 7 mg/g versus those who had an ACR > 7 mg/g, no significant difference was found in frequency of use of metformin, spironolactone, or oral contraceptives.ConclusionIn women with PCOS, an ACR > 7 mg/g was strongly associated with the metabolic syndrome, high blood pressure, and elevated alanine aminotransferase levels. It may be useful to consider ACR > 7 mg/g as an associated sign of the presence of metabolic syndrome in women with PCOS. (Endocr Pract. 2008;14: 193-200)     

Obesity and Cardiovascular Disease Risk Factors in Firefighters: A Prospective Cohort Study

Objective: Obesity, despite being a significant determinant of fitness for duty, is reaching epidemic levels in the workplace. Firefighters’ fitness is important to their health and to public safety. Research Methods and Procedures: We examined the distribution of BMI and its association with major cardiovascular disease (CVD) risk factors in Massachusetts firefighters who underwent baseline (1996) and annual medical examinations through a statewide medical surveillance program over 5 years of follow‐up. We also evaluated firefighters’ weight change over time. Results: The mean BMI among 332 firefighters increased from 29 at baseline to 30 at the follow‐up examination (2001), and the prevalence of obesity increased from 35% to 40%, respectively (p < 0.0001). In addition, the proportion of firefighters with extreme obesity increased 4‐fold at follow‐up (from 0.6% to 2.4%, p < 0.0001). Obese firefighters were more likely to have hypertension (p = 0.03) and low high‐density lipoprotein‐cholesterol (p = 0.01) at follow‐up. Firefighters with extreme obesity had an average of 2.1 CVD risk factors (excluding obesity) in contrast to 1.5 CVD risk factors for normal‐weight firefighters (p = 0.02). Finally, on average, normal‐weight firefighters gained 1.1 pounds, whereas firefighters with BMI ≥ 35 gained 1.9 pounds per year of active duty over 5 years of follow‐up. Discussion: Obesity is a major concern among firefighters and shows worsening trends over time. Periodic medical evaluations coupled with exercise and dietary guidelines are needed to address this problem, which threatens firefighters’ health and may jeopardize public safety.     

Risk Factors of Developmental Defects of Enamel-A Prospective Cohort Study

Background and objective

Current studies on the aetiology of developmental defects of enamel (DDE) are subject to recall bias because of the retrospective collection of information. Our objective was to investigate potential risk factors associated with the occurrence of DDE through a prospective cohort study.

Methods

Using a random community sample of Hong Kong children born in 1997, we performed a cohort study in which the subjects’ background information, medical and dental records were prospectively collected. A clinical examination to identify DDE was conducted in 2010 when the subjects were 12 years old. The central incisor, lateral incisor and first molar in each quadrant were chosen as the index teeth and were examined ‘wet’ by two trained and calibrated examiners using the modified FDI (DDE) Index.

Results

With a response rate of 74.9%, the 514 examined subjects had matched data for background information. Diffuse opacites were the most common type of DDE. Of the various possible aetiological factors considered, only experience of severe diseases during the period 0–3 years was associated with the occurrence of ‘any defect’ (p = 0.017) and diffuse opacities (p = 0.044). The children with experience of severe diseases before 3 years of age were 7.89 times more likely to be affected by ‘any defect’ compared with those who did not have the experience (OR 7.89; 95% CI 1.07, 58.14; p = 0.043). However, after adjusting for confounding factors, the association no longer existed.

Conclusion

No variables could be identified as risk factors of DDE in this Hong Kong birth cohort.     

Risk of Adverse Pregnancy Outcomes among Women Practicing Poor Sanitation in Rural India: A Population-Based Prospective Cohort Study

BackgroundThe importance of maternal sanitation behaviour during pregnancy for birth outcomes remains unclear. Poor sanitation practices can promote infection and induce stress during pregnancy and may contribute to adverse pregnancy outcomes (APOs). We aimed to assess whether poor sanitation practices were associated with increased risk of APOs such as preterm birth and low birth weight in a population-based study in rural India.ConclusionsThis study provides the first evidence, to our knowledge, that poor sanitation is associated with a higher risk of APOs. Additional studies are required to elucidate the socio-behavioural and/or biological basis of this association so that appropriate targeted interventions might be designed to support improved birth outcomes in vulnerable populations. While it is intuitive to expect that caste and poverty are associated with poor sanitation practice driving APOs, and we cannot rule out additional confounders, our results demonstrate that the association of poor sanitation practices (open defecation) with these outcomes is independent of poverty. Our results support the need to assess the mechanisms, both biological and behavioural, by which limited access to improved sanitation leads to APOs.     

BMI-Associated Alleles Do Not Constitute Risk Alleles for Polycystic Ovary Syndrome Independently of BMI: A Case-Control Study

Introduction

Polycystic Ovary Syndrome (PCOS) has a strong genetic background and the majority of patients with PCOS have elevated BMI levels. The aim of this study was to determine to which extent BMI-increasing alleles contribute to risk of PCOS when contemporaneous BMI is taken into consideration.

Methods

Patients with PCOS and controls were recruited from the United Kingdom (563 cases and 791 controls) and The Netherlands (510 cases and 2720 controls). Cases and controls were of similar BMI. SNPs mapping to 12 BMI-associated loci which have been extensively replicated across different ethnicities, i.e., BDNF, FAIM2, ETV5, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18, were studied in association with PCOS within each cohort using the additive genetic model followed by a combined analysis. A genetic allelic count risk score model was used to determine the risk of PCOS for individuals carrying increasing numbers of BMI-increasing alleles.

Results

None of the genetic variants, including FTO and MC4R, was associated with PCOS independently of BMI in the meta-analysis. Moreover, no differences were observed between cases and controls in the number of BMI-risk alleles present and no overall trend across the risk score groups was observed.

Conclusion

In this combined analysis of over 4,000 BMI-matched individuals from the United Kingdom and the Netherlands, we observed no association of BMI risk alleles with PCOS independent of BMI.     

Risk of Cardiovascular Events in Mothers of Women with Polycystic Ovary Syndrome

ObjectiveTo assess the prevalence of cardiovascular events in an older population of women with polycystic ovary syndrome (PCOS).MethodsWe took advantage of the high heritability of PCOS and determined the probable PCOS status of mothers of women with PCOS. The prevalence of cardiovascular events was then determined in these mothers with and without PCOS. In a single endocrine clinic, 308 women with PCOS were interviewed about their mothers’ medical history, and the mothers themselves were interviewed if available. The interview addressed menstrual history, fertility, clinical signs of hyperandrogenism, age at incident cardiovascular event, and age at death as reported by daughters. Presence of PCOS in the mothers was defined as a history of infertility, irregular menses, or clinical signs of hyperandrogenism. A cardiovascular event was defined as fatal or nonfatal myocardial infarction, any coronary intervention, angina necessitating emergency department visits, or a cerebrovascular event.ResultsThe mothers were predominantly postmenopausal. Among 182 interviewed (n = 157) or deceased (n = 25) mothers, 59 had probable PCOS. Cardiovascular events were more common (P = .011) among mothers with PCOS (11 of 59 or 18.6%) than among non-PCOS mothers (5 of 123 or 4.1%). After adjustments were made for age and race, probable PCOS was an independent predictor of cardiovascular events (odds ratio, 5.41; 95% confidence interval, 1.78 to 16.40). Cardiovascular events occurred at an early age in mothers of women with PCOS, particularly mothers with probable PCOS themselves.ConclusionPCOS-affected mothers of women with PCOS have a higher risk for cardiovascular events in comparison with non-PCOS mothers, and cardiovascular events appear to occur at an earlier than expected age in mothers with PCOS. (Endocr Pract. 2008;14:1084-1094)     

Increased Risk of Acute Coronary Syndrome among Patients with Urinary Stone Disease: A Nationwide Population-Based Cohort Study

Background/Objectives

Urinary stones (US) are associated with systemic metabolic and endocrine disorders that share risk factors typically associated with acute coronary syndrome (ACS).

Methods

For this investigation, 30 142 patients with US were set as the research group, and 121 768 randomly selected patients were set as the comparison group through frequency matching by age, sex, and index year. Each patient was individually tracked to identify those who developed ACS during the follow-up period. Cox proportional hazards regression and the Kaplan-Meier method were adopted to calculate the hazard ratios of ACS risk and plot the survival curve.

Results

Overall, 275 (13.4 per 10 000 person-y) and 736 events (9.1 per 10 000 person-y) were observed among patients in the research and comparison cohorts, respectively. The patients with US had a substantially lower ACS-free survival rate compared with that of the patients in the comparison cohort (P<.001). After adjusting for potential risk factors, the patients with US were observed to have a 1.22-fold higher risk of ACS compared with patients in the comparison cohort (95% confidence interval = 1.05–1.40, P<.001), particularly among younger patients.

Conclusions

The results indicate that US is associated with increased risk of developing ACS, particularly among young (≤49 years) and male adults. Future studies should examine the possible mechanisms of US-related ACS morbidity by conducting multicenter recruitment and measurements of laboratory data.     

Obesity,Metabolic Syndrome and Risk of Atrial Fibrillation: A Swedish,Prospective Cohort Study

AimWe aimed to investigate whether different measures of obesity could similarly predict atrial fibrillation, and whether the atrial fibrillation risk associated with obesity is dependent on presence of metabolic syndrome.ResultsDuring a mean follow-up of 13.6 years, 285 incident atrial fibrillation cases were recorded. One standard deviation increment of each obesity measure was associated with increased atrial fibrillation risk as: body mass index 1.25 (1.12 – 1.40), waist circumference 1.35 (1.19 – 1.54) and sagittal abdominal diameter 1.28 (1.14 – 1.44). Compared to normal weight subjects without metabolic syndrome, increased atrial fibrillation risk was noted for overweight subjects with metabolic syndrome, 1.67 (1.16 – 2.41), obese subjects without metabolic syndrome, 1.75 (1.11 – 2.74) and obese subjects with metabolic syndrome, 1.92 (1.34 – 2.74). Compared to subjects with normal waist circumference without metabolic syndrome, subjects with elevated waist circumference and metabolic syndrome suffered increased atrial fibrillation risk, 2.03 (1.44 – 2.87).ConclusionsBody mass index, waist circumference and sagittal abdominal diameter could similarly predict atrial fibrillation. Obesity was associated with an increased atrial fibrillation risk regardless of metabolic syndrome, whereas overweight and elevated waist circumference was associated with increased atrial fibrillation risk only if metabolic syndrome was present.     

The Continuum of Maternal Sepsis Severity: Incidence and Risk Factors in a Population-Based Cohort Study

Objective

To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.

Methods

This retrospective cohort study used linked hospital discharge and vital statistics records data for 1,622,474 live births in California during 2005–2007. Demographic and clinical factors were adjusted using multivariable logistic regression with robust standard errors.

Results

1598 mothers developed sepsis; incidence of all sepsis was 10 per 10,000 live births (95% CI = 9.4–10.3). Women had significantly increased adjusted odds (aOR) of developing sepsis if they were older (25–34 years: aOR = 1.29; ≥35 years: aOR = 1.41), had ≤high-school education (aOR = 1.63), public/no-insurance (aOR = 1.22) or a cesarean section (primary: aOR = 1.99; repeat: aOR = 1.25). 791 women progressed to severe sepsis; incidence of severe sepsis was 4.9 per 10,000 live births (95% CI = 4.5–5.2). Women had significantly increased adjusted odds of progressing to severe sepsis if they were Black (aOR = 2.09), Asian (aOR = 1.59), Hispanic (aOR = 1.42), had public/no-insurance (aOR = 1.52), delivered in hospitals with <1,000 births/year (aOR = 1.93), were primiparous (aOR = 2.03), had a multiple birth (aOR = 3.5), diabetes (aOR = 1.47), or chronic hypertension (aOR = 8.51). Preeclampsia and postpartum hemorrhage were also significantly associated with progression to severe sepsis (aOR = 3.72; aOR = 4.18). For every cumulative factor, risk of uncomplicated sepsis increased by 25% (95% CI = 17.4–32.3) and risk of progression to severe sepsis/septic shock increased by 57% (95% CI = 40.8–74.4).

Conclusions

The rate of severe sepsis was approximately twice the 1991–2003 national estimate. Risk factors identified are relevant to obstetric practice given their cumulative risk effect and the apparent increase in severe sepsis incidence.     

Preeclampsia as a Risk Factor for Diabetes: A Population-Based Cohort Study

Background

Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.

Methods and Findings

We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.

Conclusions

Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors'' Summary     

COPD and the Risk of Tuberculosis - A Population-Based Cohort Study

Background

Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality.

Methods and Findings

All individuals ≥40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987–2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989–2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1).

Conclusions

This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies.     

Serum Urate,Metabolic Syndrome,and Cardiovascular Risk Factors. A Population-Based Study

We studied the associations between serum urate levels (determined in 503 subjects from a population of 1,344 subjects living in northern Madrid) and both the metabolic syndrome (MS) (defined by the Adult Treatment Panel III criteria) and C-reactive protein (CRP, determined in 382 subjects). MS was diagnosed in 25% (95%CI, 21–28%) and was associated with hyperuricemia (p<0.001). There was a graded increase in serum urate levels with increasing number of MS components. Urate concentrations significantly correlated with waist circumference (r=0,455, p<0.01). Serum urate was not independently associated with CRP levels. This study shows that serum urate levels are associated with the presence of MS and each of its features.     

The Risk of Asthma in Patients with Ankylosing Spondylitis: A Population-Based Cohort Study

BackgroundThe relationship between asthma and ankylosing spondylitis (AS) is controversial. We examined the risk of asthma among AS patients in a nationwide population.MethodsWe conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The cohort included 5,974 patients newly diagnosed with AS from 2000 to 2010. The date of diagnosis was defined as the index date. A 4-fold of general population without AS was randomly selected frequency matched by age, gender and the index year. The occurrence and hazard ratio (HR) of asthma were estimated by the end of 2011.ResultsThe overall incidence of asthma was 1.74 folds greater in the AS cohort than in the non-AS cohort (8.26 versus 4.74 per 1000 person-years) with a multivariable Cox method measured adjusted HR of 1.54 (95% confidence interval (CI), 1.34–1.76). The adjusted HR of asthma associated with AS was higher in women (1.59; 95% CI, 1.33–1.90), those aged 50–64 years (1.66; 95% CI, 1.31–2.09), or those without comorbidities (1.82; 95% CI, 1.54–2.13).ConclusionPatients with AS are at a higher risk of developing asthma than the general population, regardless of gender and age. The pathophysiology needs further investigation.     

Association Study of Gene LPP in Women with Polycystic Ovary Syndrome

Background

Previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese population has found that SNPs in LPP gene were nominally significant in PCOS patients (P around 10E-05). Replication of the GWAS was applied to further confirm the relationship between LPP gene and PCOS.

Methods

Three polymorphisms of LPP gene (rs715790, rs4449306, rs6782041) were selected and replicated in additional 1132 PCOS cases and 1142 controls. Genotyping of LPP gene was carried out by Taqman-MGB method.

Results

In rs715790, the allele frequency is significantly different between the PCOS group and the control group. Meta-analysis showed that the allele frequencies of the three SNPs rs715790 (P_meta = 1.89E-05, OR = 1.23), rs4449306 (P_meta = 3.0E-04, OR = 1.10), rs6782041 (P_meta = 2.0E-04, OR = 1.09), were significantly different between PCOS cases and controls.

Conclusions

Our results suggest that LPP gene might be a novel candidate for PCOS.     

Quality of Life and Associated Socio-Clinical Factors after Encephalitis in Children and Adults in England: A Population-Based,Prospective Cohort Study

Objective

We sought to measure HRQoL in all-cause encephalitis survivors and assess the impact of various socio-clinical factors on outcome.

Methods

We used a prospective cohort study design, using the short-form 36 (SF-36) to measure the HRQoL in patients 15 years and older, and the short-form 10 (SF-10) for patients less than 15 years old. We posted questionnaires to individuals six months after discharge from hospital. All scores were normalised to the age- and sex-matched general population. We used multivariate statistical analysis to assess the relative association of clinical and socio-demographic variables on HRQoL in adults.

Results

Of 109 individuals followed-up, we received 61 SF-36 and twenty SF-10 questionnaires (response rate 74%). Patients scored consistently worse than the general population in all domains of the SF-36 and SF-10, although there was variation in individual scores. Infectious encephalitis was associated with the worst HRQoL in those aged 15 years and over, scoring on average 5.64 points less than immune-mediated encephalitis (95% CI −8.77– −2.89). In those aged less than 15 years the worst quality of life followed encephalitis of unknown cause. Immuno compromise, unemployment, and the 35–44 age group all had an independent negative association with HRQoL. A poor Glasgow Outcome Score was most strongly associated with a poor HRQoL. Less than half of those who had made a ‘good’ recovery on the score reported a HRQoL equivalent to the general population.

Conclusions

Encephalitis has adverse effects on the majority of survivors’ wellbeing and quality of life. Many of these adverse consequences could be minimised by prompt identification and treatment, and with better rehabilitation and support for survivors.     

Common Variant rs9939609 in Gene FTO Confers Risk to Polycystic Ovary Syndrome

Background

Fat mass and obesity-associated gene (FTO) has been associated with obesity, especially the common variant rs9939609. Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder and over 50% of patients are overweight/obese. Thus FTO is a potential candidate gene for PCOS but their relationship is confusing and remains to be clarified in different population with a large sample size.

Method

This study was performed adopting a two-stage design by genotyping SNP rs9939609. The first set comprise of 741 PCOS and 704 control subjects, with data from our previous GWAS. The second phase of replication study was performed among another independent group of 2858 PCOS and 2358 control subjects using TaqMan-MGB probe assay. All subjects are from Han Chinese.

Results

The less meaningful association of FTO rs9939609 and PCOS discovered in GWAS (P = 2.47E-03), was further confirmed in the replication study (P = 1.86E-09). Using meta-analysis, the P-meta value has reached 6.89E-12, over-exceeding the genome-wide association level of 5.00E-8. By combination, the P value was 1.26E-11 and after BMI adjustment it remained significant(P = 1.82E-06). To further elucidate whether this association is resulted from obesity or PCOS per se, the samples were divided into two groups–obese and non-obese PCOS, and the results were still positive in obese group (P obese = 5.81E-05, OR = 1.55), as well as in non-obese PCOS group (P non-obese = 7.06E-04, OR = 1.28).

Conclusion

Variant rs9939609 in FTO is associated with PCOS in Chinese women, not only in obese PCOS subjects, but also in non-obese cases.     

Risk Factors for Venous Thromboembolism in 1.3 Million Pregnancies: A Nationwide Prospective Cohort

Objective

To quantify risk factors for venous thromboembolism during pregnancy and the puerperal period.

Design

In a nationwide prospective cohort study we followed pregnant and puerperal women in Denmark from 1995 to 2009 for venous thromboembolism. Information on risk factors and confounders was retrieved from national registries. The diagnosis of venous thromboembolism was confirmed through medical charts. We calculated adjusted incidence rates per 10,000 women years and used Poisson regression to estimate effects during pregnancy and the puerperal period.

Results

We studied 1,297,037 pregnancies and related puerperal periods, during which there were 748 venous thromboembolisms. The incidence rate for venous thromboembolism during a pregnancy with and without hospitalization for hyperemesis was 15.2/10,000 yr and 6.3/10,000 yr, respectively, (adjusted rate ratio: 2.5 (95%-confidence interval; 1.4–4.5)). The incidence rate among women with multiple pregnancies was 18.2/10,000 yr and 6.3/10,000 yr in singletons (adjusted rate ratio: 2.8 (1.9–4.2)). Increased risk was found with hospitalization during pregnancy or the puerperal period with incidence rates of 42.1/10.000 and 54.7/10.000, respectively, (rate ratios: 12.2 (8.7–17) and 5.9 (4.0–8.8)). Women hospitalized with infections during pregnancy had incidence rates of 25.9/10,000 yr and 29.3/10,000 yr during pregnancy and the puerperal period, respectively, and of 62.7/10,000 yr if hospitalized with infection in the puerperal period. Puerperal venous thromboembolism was associated with hospitalization for preeclampsia and intrauterine growth restriction/fetal death with incidence rates of 45.8/10,000 yr and 18.3/10,000 yr, respectively (rate ratio: 5.0 (3.1–7.8) and 1.9 (0.9–4.4)). Additionally puerperal venous thromboembolism was associated with obesity, elective and acute caesarean sections and major postpartum bleeding with incidence rates of 25.5/10,000 yr, 23.2/10,000 yr, 34.0/10,000 yr and 20.3/10,000 yr, respectively (rate ratios 1.7 (1.1–2.7), 2.1 (1.4–3.1), 3.0 (2.3–4.0) and 1.4 (1.0–2.1)).

Conclusions

Important risk factors for venous thromboembolism during pregnancy or the puerperal period were hospitalization, infection, hyperemesis, multiple pregnancies, preeclampsia, obesity, caesarean section, major postpartum bleeding, and intrauterine growth restriction or fetal death.     

Cancer Risk in Children and Adolescents with Birth Defects: A Population-Based Cohort Study

Objective

Birth defects are an increasing health priority worldwide, and the subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may be an added burden in this vulnerable group of children, but studies to date have provided inconsistent findings. This study assessed the risk for cancer in children and young adolescents with major birth defects.

Methods and Findings

This retrospective, statewide, population-based, cohort study was conducted in three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young adolescents (0 through 14 years of age) with selected major, non-chromosomal birth defects or chromosomal anomalies was compared to a reference cohort of 147,940 children without birth defects randomly sampled from each state’s births and frequency matched by year of birth. The primary outcome was rate of cancer prior to age 15 years, by type of cancer and type of birth defect. The incidence of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth defects (123 cases of cancer) compared to the reference cohort; the incidence rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the excess risk varied markedly by type of birth defect. Increased risks were seen in children with microcephaly, cleft palate, and selected eye, cardiac, and renal defects. Cancer risk was not increased with many common birth defects, including hypospadias, cleft lip with or without cleft palate, or hydrocephalus.

Conclusion

Children with some structural, non-chromosomal birth defects, but not others, have a moderately increased risk for childhood cancer. Information on such selective risk can promote more effective clinical evaluation, counseling, and research.