Predictors of poor perinatal outcome following maternal perception of reduced fetal movements--a prospective cohort study

Background

Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency.

Objective

To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM).

Design

Prospective cohort study.

Methods

305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression.

Results

22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31–38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01–1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94–0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02–0.99) were independently related to pregnancy outcome. hPL was related to placental mass.

Conclusion

Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.     

Widowhood and mortality: a meta-analysis

Background

While the "widowhood effect" is well known, there is substantial heterogeneity in the magnitude of effects reported in different studies. We conducted a meta-analysis of widowhood and mortality, focusing on longitudinal studies with follow-up from the time of bereavement.

Methods and Findings

A random-effects meta-analysis was conducted to calculate the overall relative risk (RR) for subsequent mortality among 2,263,888 subjects from 15 prospective cohort studies. We found a statistically significant positive association between widowhood and mortality, but the widowhood effect was stronger in the period earlier than six months since bereavement (overall RR = 1.41, 95% CI: 1.26, 1.57) compared to the effect after six months (overall RR = 1.14, 95% CI: 1.10, 1.18). Meta-regression showed that the widowhood effect was not different for those aged younger than 65 years compared to those older than 65 (P = 0.25). There was, however, a difference in the magnitude of the widowhood effect by gender; for women the RR was not statistically significantly different from the null (overall RR = 1.04, 95% CI: 1.00, 1.08), while it was for men (overall RR = 1.23, 95% CI: 1.18, 1.28).

Conclusions

The results suggest that further studies should focus more on the mechanisms that generate this association especially among men.     

Maternal and Perinatal Outcomes of Twin Pregnancy in 23 Low- and Middle-Income Countries

Background

Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.

Methods

We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.

Results

279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60–2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40–4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95–6.62) and stillbirth (AOR 1.22, 95% CI 0.58–2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.

Conclusions

Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.     

High incidence of unplanned pregnancy after antiretroviral therapy initiation: findings from a prospective cohort study in South Africa

Background

Increased fertility rates in HIV-infected women receiving antiretroviral therapy (ART) have been attributed to improved immunological function; it is unknown to what extent the rise in pregnancy rates is due to unintended pregnancies.

Methods

Non-pregnant women ages 18–35 from four public-sector ART clinics in Johannesburg, South Africa, were enrolled into a prospective cohort and followed from August 2009–March 2011. Fertility intentions, contraception and pregnancy status were measured longitudinally at participants'' routine ART clinic visits.

Findings

Of the 850 women enrolled, 822 (97%) had at least one follow-up visit and contributed 745.2 person-years (PY) at-risk for incident pregnancy. Overall, 170 pregnancies were detected in 161 women (incidence rate [IR]: 21.6/100 PY [95% confidence interval (CI): 18.5–25.2]). Of the 170 pregnancies, 105 (62%) were unplanned. Unmet need for contraception was 50% higher in women initiating ART in the past year as compared to women on ART>1 year (prevalence ratio 1.5 [95% CI: 1.1–2.0]); by two years post-ART initiation, nearly one quarter of women had at least one unplanned pregnancy. Cumulative incidence of pregnancy was equally high among recent ART initiators and ART experienced participants: 23.9% [95% CI: 16.4–34.1], 15.9% [12.0–20.8], and 21.0% [16.8–26.1] for women on ART 0–1 yr, >1 yr–2 yrs, and >2 yrs respectively (log-rank, p = 0.54). Eight hormonal contraceptive failures were detected [IR: 4.4 [95% CI: 2.2–8.9], 7/8 among women using injectable methods. Overall 47% (80/170) of pregnancies were not carried to term.

Conclusions

Rates of unintended pregnancies among women on ART are high, including women recently initiating ART with lower CD4 counts and higher viral loads. A substantial burden of pregnancy loss was observed. Integration of contraceptive services and counselling into ART care is necessary to reduce maternal and child health risks related to mistimed and unwanted pregnancies. Further research into injectable contraceptive failures on ART is warranted.     

Smoking during pregnancy is associated with a decreased incidence of obstetric anal sphincter injuries in nulliparous women

Background

Smoking is a modifiable lifestyle factor that has been shown to be associated with adverse perinatal outcomes and to have adverse health and dose-dependent connective tissue effects. The objective of this study was to examine whether smoking during pregnancy was associated with the incidence of obstetric anal sphincter injuries (OASIS) among six birthweight groups in singleton vaginal deliveries, considering nulliparous and multiparous women separately between 1997 and 2007 in Finland.

Methodology

A retrospective population-based register study. Populations included women with spontaneous singleton vaginal deliveries, consisting of all 213,059 nulliparous and all 288,391 multiparous women. Incidence of OASIS (n = 2,787) between smoking status groups was adjusted using logistic regression analyses.

Principal Findings

Of the nulliparous women, 13.1% were smokers, 3.6% had given up smoking during the first trimester of their pregnancy and 81.1% were non-smokers. Among these groups 0.7%, 0.9% and 1.1%, respectively suffered OASIS (p≤0.001). Nulliparous women who smoked had a 28% (95% CI 16–38%, p≤0.001) lower risk of OASIS compared to non-smokers, when adjusting for background variables. In multiparous women, the overall frequencies of OASIS were much lower (0.0–0.2%). A similar inverse relationship between OASIS rates and smoking was significant in pooled univariate analysis of multiparous women, but multivariate analysis revealed statistically insignificant results between non-smokers and smokers.

Conclusions

Nulliparous women who were smokers had a 28% lower incidence of OASIS. However, smoking during pregnancy cannot be recommended since it has shown to be associated with other adverse pregnancy outcomes and adverse health effects. The observed association warrants clinical repetition studies and, if confirmed, also in vitro studies focusing on connective tissue properties at a molecular and cellular level.     

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background

Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.

Methods and Findings

Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).

Conclusions

In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).     

Efficacy and safety of abciximab in diabetic patients who underwent percutaneous coronary intervention with thienopyridines loading: a meta-analysis

Background

It has been controversial whether abciximab offered additional benefits for diabetic patients who underwent percutaneous coronary intervention (PCI) with thienopyridines loading.

Methods

MEDLINE, EMBASE, the Cochrane library clinical trials registry, ISI Science Citation Index, ISI Web of Knowledge and China National Knowledge Infrastructure (CNKI) were searched, supplemented with manual-screening for relevant publications. Quantitative meta-analyses were performed to assess differences between abciximab groups and controls with respect to post-PCI risk of major cardiac events (MACEs), angiographic restenosis and bleeding complications.

Results

9 trials were identified, involving 2,607 diabetic patients receiving PCI for coronary artery diseases. Among those patients who underwent elective PCI or primary PCI, pooling results showed that abciximab did not significantly reduce risks of MACEs (for elective-PCI patients: RR_1-month: 0.93, 95% CI: 0.60–1.44; RR_1-year: 0.95, 95% CI: 0.81–1.11; for primary-PCI patients: RR_1-month: 1.05, 95% CI: 0.70–1.57; RR_1-year: 0.98, 95% CI: 0.80–1.21), nor all-cause mortality, re-infarction and angiographic restenosis in either group. The only beneficial effect by abciximab appeared to be a decrease 1-year TLR (target lesion revascularization) risk in elective-PCI patients (RR1-year: 0.83, 95% CI: 0.70–0.99). Moreover, occurrence of minor bleeding complications increased in elective-PCI patients treated with abciximab (RR: 2.94, 95% CI: 1.68–5.13, P<0.001), whereas major bleedings rate was similar (RR: 0.83, 95% CI: 0.27–2.57).

Conclusions

Concomitant dosing of abciximab and thienopyridines provides no additional benefit among diabetic patients who underwent PCI; this conclusion, though, needs further confirmation in larger studies.     

30 Year patterns of mortality in Tobago, West Indies, 1976-2005: impact of glucose intolerance and alcohol intake

Objectives

To determine the main predictors of all-cause and cardiovascular (CV) mortality in a rural West Indian population in Plymouth, Tobago over 30 years.

Methods

Questionnaire survey for CV risk factors and alcohol consumption patterns administered at baseline in 1976 with 92.5% response rate. 831/832 patients were followed up until 2005 or death.

Results

Hypertension (>140/90 mm Hg) was prevalent in 48% of men and 44% of women, and 21% of men and 17% of women had diabetes. Evidence showed most predictors for all cause and cardiovascular mortality having the main effects at ages <60 years, (p-value for interaction<0.01) but no risk factors having sex-specific effects on mortality. The main predictors of all-cause mortality at age <60 years in the fully adjusted model were high sessional alcohol intake (hazard ratio (HR) 2.04, 95% CI 1.10-3.80), severe hypertension >160/95 mm Hg (HR 1.68, 95% CI 1.09-2.60), diabetes (HR 3.28, 95% CI 1.89-5.69), and BMI (HR 1.04, 95% CI 1.00-1.07). The main predictors of cardiovascular mortality were similar in the fully adjusted model: high sessional alcohol intake (HR 2.47 95% CI 1.10-5.57), severe hypertension (HR 2.78 95% CI 1.56-4.95), diabetes (HR 3.68 95% CI 1.77-7.67) and additionally LVH, (HR 5.54 95% CI 1.38-22.26), however BMI did not show independent effects. For men, high sessional alcohol intake explains 27% of all cause mortality, and 40% of cardiovascular mortality at age <60 yrs. In adults aged <60 years, the attributable risk fraction for IGT/Diabetes and all cause mortality and cardiovascular mortality is 28% in women vs. 11% in men, and 22% in women vs. 6% in men respectively.

Conclusions

In this Afro-Caribbean population we found that a major proportion of deaths are attributable to high sessional alcohol intake (in males), diabetes, and hypertension and these risk factors primarily operate in those below 60 years.     

Marital status and mortality among middle age and elderly men and women in urban Shanghai

Background

Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality.

Methods

We examined the association of marital status with mortality using data from the Shanghai Women''s Health Study (1996–2009) and Shanghai Men''s Health Study (2002–2009), two population-based cohort studies of 74,942 women aged 40–70 years and 61,500 men aged 40–74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI).

Results

Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality.

Conclusions

Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.     

Cytomegalovirus viremia as a risk factor for mortality prior to antiretroviral therapy among HIV-infected gold miners in South Africa

Background

Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV.

Methods

Using a cohort of mineworkers with stored plasma samples, we investigated the association between CMV DNA concentration and mortality prior to antiretroviral therapy availability.

Results

Among 1341 individuals (median CD4 count 345 cells/µl, 70% WHO stage 1 or 2, median follow-up 0.9 years), 70 (5.2%) had CMV viremia at baseline; 71 deaths occurred. In univariable analysis CMV viremia at baseline was associated with a three-fold increase in mortality (hazard ratio [HR] 3.37; 95% confidence intervals [CI] 1.60, 7.10). After adjustment for CD4 count, WHO stage and HIV viral load (N = 429 with complete data), the association was attenuated (HR 2.27; 95%CI 0.88, 5.83). Mortality increased with higher CMV viremia (≥1,000 copies/ml vs. no viremia, adjusted HR 3.65, 95%CI: 1.29, 10.41). Results were similar using time-updated CMV viremia.

Conclusions

High copy number, subclinical CMV viremia was an independent risk factor for mortality among male HIV-infected adults in South Africa with relatively early HIV disease. Studies to determine whether anti-CMV therapy to mitigate high copy number viremia would increase lifespan are warranted.     

Influenza-related mortality trends in Japanese and American seniors: evidence for the indirect mortality benefits of vaccinating schoolchildren

Background

The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US.

Methods

We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978–1994) and after the program was discontinued (1995–2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control.

Results

We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17–51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400–1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population.

Conclusions

The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors.     

Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis

Background

Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes.

Methodology and Principal Findings

We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93–1.04), stroke (RR, 0.89; 95% CI,0.78–1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93–1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96–1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95–1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97–1.15), cancer (RR, 1.08; 95%CI, 0.98–1.21), vascular death (RR, 0.94; 95%CI,0.88–1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97–1.15).

Conclusion/Significance

Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality.     

Sex differences in step count-blood pressure association: a preliminary study in type 2 diabetes

Background

Walking and cardiovascular mortality are inversely associated in type 2 diabetes, but few studies have objectively measured associations of walking with individual cardiovascular risk factors. Such information would be useful for “dosing” daily steps in clinical practice. This study aimed to quantify decrements in blood pressure and glycated hemoglobin (A1C) per 1,000 daily step increments.

Methodology/Principal Findings

Two hundred and one subjects with type 2 diabetes underwent assessments of step counts (pedometer-measured), blood pressure, A1C and anthropometric parameters. Due to missing data, the final analysis was conducted on 83 women and 102 men, with a mean age of 60 years. Associations of daily steps with blood pressure and A1C were evaluated using sex-specific multivariate linear regression models (adjusted for age, ethnicity, and BMI). Potential sex differences were confirmed in a combined model (women and men) with interaction terms. Mean values for daily steps, blood pressure, A1C and BMI were 5,357 steps/day; 137/80 mm Hg; 7.7% and 30.4 kg/m² respectively. A 1,000 daily step increment among women was associated with a −2.6 (95% CI: −4.1 to −1.1) mm Hg change in systolic and a −1.4 (95% CI: −2.2 to −0.6) mm Hg change in diastolic blood pressure. Among men, corresponding changes were −0.7 (95% CI: −2.1 to 0.7) and −0.6 (95% CI: −1.4 to 0.3) mm Hg, respectively. Sex differences were confirmed in combined models. Step counts and A1C did not demonstrate clinically important associations.

Conclusions/Significance

A 1,000 steps/day increment is associated with important blood pressure decrements among women with type 2 diabetes but the data were inconclusive among men. Targeted “dose increments” of 1,000 steps/day in women may lead to measurable blood pressure reductions. This information may be of potential use in the titration or “dosing” of daily steps. No associations were found between step count increments and A1C.     

Trends in breast cancer mortality in Sweden before and after implementation of mammography screening

Background

Incidence-based mortality modelling comparing the risk of breast cancer death in screened and unscreened women in nine Swedish counties has suggested a 39% risk reduction in women 40 to 69 years old after introduction of mammography screening in the 1980s and 1990s.

Objective

We evaluated changes in breast cancer mortality in the same nine Swedish counties using a model approach based on official Swedish breast cancer mortality statistics, robust to effects of over-diagnosis and treatment changes. Using mortality data from the NordCan database from 1974 until 2003, we estimated the change in breast cancer mortality before and after introduction of mammography screening in at least the 13 years that followed screening start.

Results

Breast mortality decreased by 16% (95% CI: 9 to 22%) in women 40 to 69, and by 11% (95% CI: 2 to 20%) in women 40 to 79 years of age.

Discussion

Without individual data it is impossible to completely separate the effects of improved treatment and health service organisation from that of screening, which would bias our results in favour of screening. There will also be some contamination of post-screening mortality from breast cancer diagnosed prior to screening, beyond our attempts to adjust for delayed benefit. This would bias against screening. However, our estimates from publicly available data suggest considerably lower benefits than estimates based on comparison of screened versus non-screened women.     

Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study

Purpose

Residing in deprived areas may increase risk of mortality beyond that explained by a person''s own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors.

Methods

In the longitudinal NIH-AARP Study, we analyzed data from healthy participants, ages 50–71 years at study baseline (1995–1996). Deaths (n = 33831) were identified through December 2005. Information on census tracts was obtained from the 2000 US Census. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of neighborhood deprivation.

Results

Participants in the highest quintile of deprivation had elevated risks for overall mortality (HR_men = 1.17, 95% CI: 1.10, 1.24; HR_women = 1.13, 95% CI: 1.05, 1.22) and marginally increased risk for cancer deaths (HR_men = 1.09, 95% CI: 1.00, 1.20; HR_women = 1.09, 95% CI: 0.99, 1.22). CVD mortality associations appeared stronger in men (HR = 1.33, 95% CI: 1.19, 1.49) than women (HR = 1.18, 95% CI: 1.01, 1.38). There was no evidence of an effect modification by education.

Conclusion

Higher neighborhood deprivation was associated with modest increases in all-cause, cancer- and CVD-mortality after accounting for many established risk factors.     

Sickness absence due to otoaudiological diagnoses and risk of disability pension: a nationwide Swedish prospective cohort study

Background

Hearing difficulties are a large public health problem. Knowledge is scarce regarding risk of disability pension among people who have been sickness absent due to these difficulties.

Methods

A cohort including all 4,687,756 individuals living in Sweden in 2005, aged 20–64, and not on disability or old-age pension, was followed through 2009. Incidence rate ratios (RR) of disability pension with 95% confidence intervals (CI) were estimated using Cox proportional hazard models.

Results

In multivariable models, individuals who had a sick-leave spell due to otoaudiological diagnoses in 2005 had a 1.52-fold (95% CI: 1.43–1.62) increased risk of being granted a disability pension compared to individuals on sick leave due to other diagnoses. Hearing and tinnitus sick-leave diagnoses were associated with risk of disability pension: RR 3.38, 95% CI: 3.04–3.75, and 3.30, 95% CI: 2.95–3.68, respectively. No association was observed between sick leave due to vertigo diagnoses and disability pension whereas otological diagnoses and no sick leave were inversely associated with risk of disability pension compared to non-otoaudiological sick-leave diagnoses. Sick leave due to otoaudiological diagnoses was positively associated with risk of disability pension due to otoaudiological diagnoses and sick leave due to a tinnitus diagnosis was also associated with risk of disability pension due to mental diagnoses. The risk of disability pension among individuals with hearing or tinnitus sick-leave diagnoses was highest in the age group 35–44. Moreover, men had a slightly higher risk.

Conclusion

This large cohort study suggests an increased risk of disability pension among those with sickness absence due to otoaudiological diagnoses, particularly hearing and tinnitus diagnoses, compared to those with sickness absence due to non-otoaudiological diagnoses.     

Uterine Rupture by Intended Mode of Delivery in the UK: A National Case-Control Study

Background

Recent reports of the risk of morbidity due to uterine rupture are thought to have contributed in some countries to a decrease in the number of women attempting a vaginal birth after caesarean section. The aims of this study were to estimate the incidence of true uterine rupture in the UK and to investigate and quantify the associated risk factors and outcomes, on the basis of intended mode of delivery.

Methods and Findings

A UK national case-control study was undertaken between April 2009 and April 2010. The participants comprised 159 women with uterine rupture and 448 control women with a previous caesarean delivery. The estimated incidence of uterine rupture was 0.2 per 1,000 maternities overall; 2.1 and 0.3 per 1,000 maternities in women with a previous caesarean delivery planning vaginal or elective caesarean delivery, respectively. Amongst women with a previous caesarean delivery, odds of rupture were also increased in women who had ≥ two previous caesarean deliveries (adjusted odds ratio [aOR] 3.02, 95% CI 1.16–7.85) and <12 months since their last caesarean delivery (aOR 3.12, 95% CI 1.62–6.02). A higher risk of rupture with labour induction and oxytocin use was apparent (aOR 3.92, 95% CI 1.00–15.33). Two women with uterine rupture died (case fatality 1.3%, 95% CI 0.2–4.5%). There were 18 perinatal deaths associated with uterine rupture among 145 infants (perinatal mortality 124 per 1,000 total births, 95% CI 75–189).

Conclusions

Although uterine rupture is associated with significant mortality and morbidity, even amongst women with a previous caesarean section planning a vaginal delivery, it is a rare occurrence. For women with a previous caesarean section, risk of uterine rupture increases with number of previous caesarean deliveries, a short interval since the last caesarean section, and labour induction and/or augmentation. These factors should be considered when counselling and managing the labour of women with a previous caesarean section. Please see later in the article for the Editors'' Summary     

Is Gestational Hypertension Protective against Perinatal Mortality in Twin Pregnancies?

Background

Pregnancy-induced or gestational hypertension is a common pregnancy complication. Paradoxically, gestational hypertension has been associated with a protective effect against perinatal mortality in twin pregnancies in analytic models (logistic regression) without accounting for survival time. Whether this effect is real remains uncertain. This study aimed to validate the impact of gestational hypertension on perinatal mortality in twin pregnancies using a survival analysis approach.

Methods

This was a retrospective cohort study of 278,821 twin pregnancies, using the U.S. 1995–2000 matched multiple birth dataset (the largest dataset available for multiple births). Cox proportional hazard models were applied to estimate the adjusted hazard ratios (aHR) of perinatal death (stillbirth and neonatal death) comparing gestational hypertensive vs. non-hypertensive pregnancies controlling for maternal characteristics and twin cluster-level dependence.

Results

Comparing births in gestational hypertensive vs. non-hypertensive twin pregnancies, perinatal mortality rates were significantly lower (1.20% vs. 3.38%), so were neonatal mortality (0.72% vs. 2.30%) and stillbirth (0.48% vs. 1.10%) rates. The aHRs (95% confidence intervals) were 0.34 (0.31–0.38) for perinatal death, 0.31 (0.27–0.34) for neonatal death, and 0.45 (0.38–0.53) for stillbirth, respectively. The protective effect of gestational hypertension against perinatal death became weaker over advancing gestational age; the aHRs in very preterm (<32 weeks), mild preterm (32–36 weeks) and term (37+ weeks) births were 0.29, 0.48 and 0.76, respectively. The largest risk reductions in neonatal mortality were observed for infections and immaturity-related conditions.

Conclusions

Gestational hypertension appears to be beneficial for fetal survival in twin pregnancies, especially in those ending more prematurely or for deaths due to infections and immaturity-related conditions. Prospective studies are required to rule out the possibility of unmeasured confounders.     

The role of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence and prognosis: a meta-analysis of prospective cohort studies

Background

The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.

Methods

We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.

Results

The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients.

Conclusion

The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.     

Previous lung diseases and lung cancer risk: a systematic review and meta-analysis

Background

In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.

Methods

Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.

Results

A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22–1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97–1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).

Conclusions

Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer.