One-step vs 2-step gestational diabetes mellitus screening and pregnancy outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: This was a systematic review and meta-analysis comparing maternal and neonatal outcomes of patients screened with the 1-step or 2-step screening method for gestational diabetes mellitus. DATA SOURCES: PubMed, Scopus, Cochrane, ClinicalTrials.gov, and LILACS were searched from inception up to September 2022. STUDY ELIGIBILITY CRITERIA: Only randomized controlled trials were included. Studies that had overlapping populations were excluded (International Prospective Register of Systematic Review registration number: CRD42022358903). METHODS: Risk ratios were computed with 95% confidence intervals by 2 authors. Unpublished data were requested. Large for gestational age was the primary outcome. RESULTS: The search yielded 394 citations. Moreover, 7 randomized controlled trials met the inclusion criteria. A total of 54,650 participants were screened for gestational diabetes mellitus by either the 1-step screening method (n=27,163) or the 2-step screening method (n=27,487). For large for gestational age, there was no significant difference found between the groups (risk ratio, 0.99; 95% confidence interval, 0.93-1.05; I2=0%). Newborns of patients who underwent 1-step screening had higher rates of neonatal hypoglycemia (risk ratio, 1.24; 95% confidence interval, 1.14-1.34; I2=0%) and neonatal intensive care unit admissions (risk ratio, 1.13; 95% confidence interval, 1.04-1.21; I2=0%) than newborns of patients who underwent 2-step screening. Patients in the 1-step screening method group were more likely to be diagnosed with gestational diabetes mellitus (risk ratio, 1.73; 95% confidence interval, 1.44-2.09; I2=80%) than patients in the 2-step screening method group. In addition, among trials that tested all patients before randomization and excluded patients with pregestational diabetes mellitus, newborns were more likely to have macrosomia (risk ratio, 1.27; 95% confidence interval, 1.21-1.34; I2=0%). Overall risk of bias assessment was of low concern. CONCLUSION: Large for gestational age did not differ between patients screened using the 1-step screening method and those screened using the 2-step screening method. However, patients randomized to the 1-step screening method had higher rates of neonatal hypoglycemia and neonatal intensive care unit admission and maternal gestational diabetes mellitus diagnosis than the patients randomized to the 2-step screening method.

A Pragmatic, Randomized Clinical Trial of Gestational Diabetes Screening.

BACKGROUND: Gestational diabetes mellitus is common and is associated with an increased risk of adverse maternal and perinatal outcomes. Although experts recommend universal screening for gestational diabetes, consensus is lacking about which of two recommended screening approaches should be used. METHODS: We performed a pragmatic, randomized trial comparing one-step screening (i.e., a glucose-tolerance test in which the blood glucose level was obtained after the oral administration of a 75-g glucose load in the fasting state) with two-step screening (a glucose challenge test in which the blood glucose level was obtained after the oral administration of a 50-g glucose load in the nonfasting state, followed, if positive, by an oral glucose-tolerance test with a 100-g glucose load in the fasting state) in all pregnant women who received care in two health systems. Guidelines for the treatment of gestational diabetes were consistent with the two screening approaches. The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section. RESULTS: A total of 23,792 women underwent randomization; women with more than one pregnancy during the trial could have been assigned to more than one type of screening. A total of 66% of the women in the one-step group and 92% of those in the two-step group adhered to the assigned screening. Gestational diabetes was diagnosed in 16.5% of the women assigned to the one-step approach and in 8.5% of those assigned to the two-step approach (unadjusted relative risk, 1.94; 97.5% confidence interval [CI], 1.79 to 2.11). In intention-to-treat analyses, the respective incidences of the other primary outcomes were as follows: large-for-gestational-age infants, 8.9% and 9.2% (relative risk, 0.95; 97.5% CI, 0.87 to 1.05); perinatal composite outcome, 3.1% and 3.0% (relative risk, 1.04; 97.5% CI, 0.88 to 1.23); gestational hypertension or preeclampsia, 13.6% and 13.5% (relative risk, 1.00; 97.5% CI, 0.93 to 1.08); and primary cesarean section, 24.0% and 24.6% (relative risk, 0.98; 97.5% CI, 0.93 to 1.02). The results were materially unchanged in intention-to-treat analyses with inverse probability weighting to account for differential adherence to the screening approaches. CONCLUSIONS: Despite more diagnoses of gestational diabetes with the one-step approach than with the two-step approach, there were no significant between-group differences in the risks of the primary outcomes relating to perinatal and maternal complications. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ScreenR2GDM ClinicalTrials.gov number, NCT02266758.).

Timing of Gestational Diabetes Diagnosis by Maternal Obesity Status: Impact on Gestational Weight Gain in a Diverse Population.

Background: We hypothesized that earlier gestational diabetes mellitus (GDM) diagnosis and treatment of high-risk women would reduce gestational weight gain (GWG) in the first trimester and overall. Materials and Methods: We evaluated timing of GDM diagnosis among 5,391 pregnant women who delivered singleton births 2010-2013 in a large diverse health maintenance organization (HMO). All GDM screening was by the same oral glucose tolerance testing protocol; GDM treatment protocols were also consistent irrespective of timing of diagnosis. Women without risk factors were universally screened at 24-28 weeks gestation (Usual). Early screening was recommended in obese and other high-risk women at the first prenatal visit; those who screened negative Early were rescreened at 24-28 weeks (Early+Usual). Results: Average GWG for all women was 12.8 kg; 10.7% of women were diagnosed with GDM. Average GWG for all women diagnosed with GDM was 10.7 kg, adjusted for gestational age. Women with EarlyGDM averaged 2.4 kg less GWG than women diagnosed with UsualGDM (p < 0.0001). Among obese women, only women diagnosed with EarlyGDM averaged overall GWG within Institute of Medicine (IOM) weight guidelines (mean 8.1 kg) and were weight neutral in the first trimester (-0.2 kg). Overall, 43% of all pregnant women exceeded IOM GWG guidelines (gained more total weight than recommended); 60% of obese women exceeded guidelines. Obese women diagnosed with GDM were less likely to exceed IOM guidelines if diagnosed earlier in pregnancy (35% EarlyGDM vs. 59% UsualGDM exceeded guidelines, p < 0.0001). Conclusion: Our results suggest that EarlyGDM diagnosis (and thus treatment) in high-risk women is beneficial for optimizing GWG.

A randomized pragmatic clinical trial of gestational diabetes screening (ScreenR2GDM): Study design, baseline characteristics, and protocol adherence.

BACKGROUND: ScreenR2GDM is a pragmatic randomized clinical trial designed to investigate if one of two gestational diabetes (GDM) screening and treatment protocols results in improved outcomes in the context of standard clinical care. METHODS: Pregnant women are randomized to one of two GDM screening strategies: 1-step: 2-h, 75 g, oral glucose tolerance test (OGTT) or 2-step: 1-h, 50 g glucose challenge test (GCT) followed by 3-h, 100 g OGTT if GCT-positive. Providers are prompted within the electronic medical record to order the assigned test but were given the option to order the alternate test. Collected data include maternal and pregnancy characteristics, GDM testing, and outcomes for mother and newborn. We describe the study design and baseline characteristics and evaluate characteristics associated with adhering to the randomized protocol. RESULTS: Baseline characteristics of the 23,792 randomized pregnancies were comparable between the two groups. Adherence to assigned test differed between the two strategies: 66.1% for 1-step and 91.7% for 2-step (p < .0001). 27% of the women randomized to receive the 1-step completed the 2-step test vs 2% randomized to the 2-step who completed the 1-step (p < .0001). Patient characteristics related to adherence included obesity, age, prior GDM, Medicaid insurance, race and nulliparity. Clinician characteristics related to adherence included provider type, age and gender. CONCLUSIONS: Both patient and provider characteristics were related to adherence to the randomized GDM screening protocol. Analytical techniques that incorporate these findings into the formal evaluation of the two protocols on GDM-associated outcomes will be necessary to account for potential biases introduced by non-adherence.

Long-Term Weight Trajectory and Risk of Hip Fracture, Falls, Impaired Physical Function, and Death.

OBJECTIVES: To determine the association between weight trajectory, health status, and mortality in older women. DESIGN: Cohort study. SETTING: Study of Osteoporotic Fractures. PARTICIPANTS: Older community-dwelling women (age: baseline (1986-88), mean 68, range 65-81; Year 20 (2006-08), mean 88, range 83-102 (N = 1,323)). MEASUREMENTS: Body weight measured repeatedly over 20 years (mean 8 times). Logistic and Cox proportional hazard models were used to evaluate whether 20-year weight trajectory measures were associated with hip fracture, falls, physical performance, and mortality. RESULTS: In models adjusted for age, clinic, calcium use, Year 20 weight, walking speed, comorbidity score, smoking, self-reported health, and walking for exercise, women with moderate weight loss (>9.0 kg) over 20 years had a 74% greater risk of death (hazard ratio (HR) = 1.74, 95% confidence interval (CI) = 1.37-2.20) in the 5 years after the Year 20 visit than those with no weight loss and more than twice the risk of hip fracture (HR = 2.56, 95% CI = 1.39-4.70). They were 3.6 times (odds ratio (OR) = 3.60, 95% CI = 1.86-6.95) as likely to have poor physical function at the Year 20 visit as women with no weight loss but no greater risk of 2 or more falls in the 1.5 years after the Year 20 visit. Weight variability and abrupt weight decline were not associated with adverse health oucomes (falls, fractures, mortality), but those in the highest quartile of variability were 2.3 times (OR = 2.26, 95% CI = 1.34-3.80) as likely to have poor physical function scores. CONCLUSION: In women surviving past 80 years of age, moderate weight loss over 20 years was associated with greater risk of hip fracture, poor physical function, and mortality but not of falls. Future work should separate voluntary from involuntary weight loss.

Associations of Smoking, Moderate Alcohol Use, and Function: A 20-Year Cohort Study of Older Women.

Objective: The objective of this study is to determine whether the health effects of smoking and moderate alcohol use persist with aging. Method: Smoking status, alcohol use, and measures of function and health were obtained from 9,704 women aged ≥65 years at baseline and over 10- and 20-year follow-up periods. Adjusted multiple linear and logistic regression and Cox proportional hazard models estimated associations. Results: Current versus never smokers had worse walking speed, self-reported health, difficulty with instrumental activities of daily living (IADLs), and depression at 10 years and higher death rates at 10 and 20 years. Moderate versus never drinkers had better grip strength, walking speed, self-reported health, and less difficulty with IADLs and were less likely to live in nursing homes at 10 years and die at 10 and 20 years. Discussion: Among aging women over 20 years, smoking is associated with worse physical function, including death, while moderate alcohol use is associated with better outcomes.

Impact of radiographic vertebral fractures on inpatient healthcare utilization in older women.

BACKGROUND: Vertebral fractures (VFx) are the most common osteoporotic fracture and are associated with higher risk of impaired function, additional fractures and death. The purpose of this analysis was to test the hypotheses that VFx are also associated with greater inpatient healthcare utilization. METHODS: We studied 4709 Caucasian women enrolled in the Study of Osteoporotic Fractures (SOF) and merged SOF cohort data with Medicare claims or Kaiser encounter data. To be included in this analysis, women had to be enrolled in Medicare Fee for Service or Kaiser as of 1/1/1991 and have radiographic information on VFx status at SOF Visit 3 (1991-92). VFx status was assessed using quantitative morphometry on lateral thoracic and lumbar spine radiographs. Prevalent VFx were defined as any height ratio>3 standard deviations below normal. Women were considered to have a clinical VFx if they reported a new diagnosis of VFx and a clinical radiographic report that confirmed that a VFx was present. Any hospitalization and the number of annualized days of hospitalization were identified through inpatient claims or encounter data. Specific hospitalizations for 5 major common reasons for hospitalizations were also examined. RESULTS: Over 5-years, 2632 (55.9%) women were hospitalized. In multivariate adjusted models, women with a prevalent radiographic VFx were 21% (95% CI, 2-44%) more likely to be hospitalized for any reason. This association was independent of a number of risk factors including smoking. The annualized rate of inpatient day was, however, similar, 1.67 and 1.48 among women with and without a VFx, respectively, p=0.49. Women with an incident clinical VFx were more likely to be hospitalized including women without evidence of a prevalent radiographic VFx (odds ratio (OR)=5.33; 95% confidence interval (CI)=1.81-15.71) and women with a prevalent radiographic VFx (OR=2.13; 95% CI, 1.05-4.33). Women with a VFx were more likely to be hospitalized specifically for hip fracture or chronic obstructive pulmonary disease (COPD) but not stroke, myocardial infarction or congestive heart failure. The association with COPD was attenuated to non-significance after adjusting for smoking. CONCLUSION: Our results extend the potential public health impact of radiographic and clinical VFx to include an increased risk of any hospitalization.

Long-term Cognitive Trajectories and Mortality in Older Women.

BACKGROUND: Few studies have examined whether change in cognition is linked to mortality. This study examined the relationship between cognitive trajectories in older age and risk of death. METHODS: We studied community-dwelling, nondemented women aged 65+ (mean age = 71) enrolled in a prospective study of aging and followed up to 25 years. A modified Mini-Mental State Examination (mMMSE) and Trail Making Task Part B (TMTB) were administered at multiple visits during follow-up. We examined the association between cognitive trajectories (analyzed by quintiles) from baseline to age 80 (n = 7,477 for mMMSE and n = 6,503 for TMTB) and all-cause mortality after age 80 using Cox regression models, both unadjusted and adjusted for education, physical activity, alcohol, depression score, current smoking and history of hypertension and diabetes. Cause of death was determined from death certificates, classified as cardiovascular, cancer and other. RESULTS: Women with greater rate of decline were older, less educated, less physically active, had higher depression score and were more likely to have a history of hypertension and diabetes (all p < .01). Participants with the greatest decline (quintile 1) had an increased risk of death (mMMSE hazard ratio [HR] = 1.28; TMTB HR = 1.43] and those with the least decline (quintile 5) had a decreased risk of death (mMMSE HR = 0.73; TMTB HR = 0.61) compared with intermediate decliners (quintiles 2-4). Cognitive trajectories were associated with cardiovascular mortality and other causes of death, but not cancer deaths. CONCLUSIONS: Our study suggests that greater decline in general cognition or executive function is associated with higher rates of mortality in oldest-old women.

A life-span behavioral mechanism relating childhood conscientiousness to adult clinical health.

OBJECTIVE: To investigate a life-span health-behavior mechanism relating childhood personality to adult clinical health. METHODS: Childhood Big Five personality traits at mean age 10, adult Big Five personality traits, adult clinically assessed dysregulation at mean age 51 (a summary of dysregulated blood glucose, blood pressure, and lipids), and a retrospective, cumulative measure of life-span health-damaging behavior (lifetime smoking, physical inactivity, and body mass index from age 20) were assessed in the Hawaii Personality and Health Cohort (N = 759). Structural equation modeling was used to test the conceptual model with direct and indirect paths from a childhood Conscientiousness factor to an adult Conscientiousness factor, life-span health-damaging behaviors, educational attainment, adult cognitive ability, and adult clinical health. RESULTS: For both men and women, childhood Conscientiousness influenced health-damaging behaviors through educational attainment, and life-span health-damaging behaviors predicted dysregulation. Childhood Conscientiousness predicted adult Conscientiousness, which did not predict any other variables in the model. For men, childhood Conscientiousness predicted dysregulation through educational attainment and health-damaging behaviors. For women, childhood Conscientiousness predicted dysregulation through educational attainment and adult cognitive ability. CONCLUSIONS: Assessing cumulative life-span health behaviors is a novel approach to the study of health-behavior mechanisms. Childhood Conscientiousness appears to influence health assessed more than 40 years later through complex processes involving educational attainment, cognitive ability, and the accumulated effects of health behaviors, but not adult Conscientiousness.

Inflammatory markers and risk of hip fracture in older white women: the study of osteoporotic fractures.

Hip fractures are the most devastating consequence of osteoporosis and impact 1 in 6 white women leading to a two- to threefold increased mortality risk in the first year. Despite evidence of inflammatory markers in the pathogenesis of osteoporosis, few studies have examined their effect on hip fracture. To determine if high levels of inflammation increase hip fracture risk and to explore mediation pathways, a case-cohort design nested in a cohort of 4709 white women from the Study of Osteoporotic Fractures was used. A random sample of 1171 women was selected as the subcohort (mean age 80.1 ± 4.2 years) plus the first 300 women with incident hip fracture. Inflammatory markers interleukin-6 (IL-6) and soluble receptors (SR) for IL-6 (IL-6 SR) and tumor necrosis factor (TNF SR1 and TNF SR2) were measured, and participants were followed for a median (interquartile range) of 6.3 (3.7, 6.9) years. In multivariable models, the hazard ratio (HR) of hip fracture for women in the highest inflammatory marker level (quartile 4) was 1.64 (95% confidence interval [CI], 1.09-2.48, p trend = 0.03) for IL-6 and 2.05 (95% CI, 1.35-3.12, p trend <0.01) for TNF SR1 when compared with women in the lowest level (quartile 1). Among women with 2 and 3-4 inflammatory markers in the highest quartile, the HR of hip fracture was 1.51 (95% CI, 1.07-2.14) and 1.42 (95% CI, 0.87-2.31) compared with women with zero to one marker(s) in the highest quartile (p trend = 0.03). After individually adjusting for seven potential mediators, cystatin-C (a biomarker of renal function) and bone mineral density (BMD) attenuated HRs among women with the highest inflammatory burden by 64% and 50%, respectively, suggesting a potential mediating role. Older white women with high inflammatory burden are at increased risk of hip fracture in part due to poor renal function and low BMD.

Long-term cognitive and functional effects of potentially inappropriate medications in older women.

BACKGROUND: The use of potentially inappropriate medications in older adults can lead to known adverse drug events, but long-term effects are less clear. We therefore conducted a prospective cohort study of older women to determine whether PIM use is associated with risk of functional impairment or low cognitive performance. METHODS: We followed up 1,429 community-dwelling women (≥ 75 years) for a period of 5 years at four clinical sites in the United States. The primary predictor at baseline was PIM use based on 2003 Beers Criteria. We also assessed anticholinergic load using the Anticholinergic Cognitive Burden scale. Outcomes included scores on a battery of six cognitive tests at follow-up and having one or more incident impairments in instrumental activities of daily living. Regression models were adjusted for baseline age, race, education, smoking, physical activity, a modified Charlson Comorbidity Index, and cognitive score. RESULTS: The mean ± SD age of women at baseline was 83.2 ± 3.3. In multivariate models, baseline PIM use and higher ACB scores were significantly associated with poorer performance in category fluency (PIM: p = .01; ACB: p = .02) and immediate (PIM: p = .04; ACB: p = .03) and delayed recall (PIM: p = .04). Both PIM use (odds ratio [OR]: 1.36 [1.05-1.75]) and higher ACB scores (OR: 1.11 [1.04-1.19]) were also strongly associated with incident functional impairment. CONCLUSIONS: The results provide suggestive evidence that PIM use and increased anticholinergic load may be associated with risk of functional impairment and low cognitive performance. More cautious selection of medications in older adults may reduce these potential risks.

Markedly different rates of incident insulin treatment based on universal gestational diabetes mellitus screening in a diverse HMO population.

OBJECTIVE: We sought to evaluate population gestational diabetes mellitus (GDM) screening results and risk for incident insulin treatment. STUDY DESIGN: Among 64,687 pregnant women universally screened for GDM from 1995 through 2010 in 2 regions of a large US health plan, we stratified women requiring insulin treatment during their pregnancy by GDM screening results (50-g glucose challenge test [GCT]), followed by a 3-hour, 100-g oral glucose tolerance test if GCT was positive. Women with GCT >200 mg/dL were evaluated separately. RESULTS: Overall, 2% of all pregnant women required insulin treatment, ranging from 0.1% (normal GCT) to 49.9% (GCT >200 mg/dL; P for trend < .0001). Women with GCT >200 mg/dL had a much higher rate of insulin treatment than women with GDM (odds ratio, 3.7; 95% confidence interval, 3.1-4.4). Risk factors for higher insulin treatment rates with GDM or GCT >200 mg/dL included obesity, race/ethnicity, and diagnosed ≤16 weeks' gestation. CONCLUSION: Our results indicate women with GCT >200 mg/dL could be reasonably treated as GDM without requiring additional oral glucose tolerance test for diagnosis.

Cystatin C and risk of hip fractures in older women.

To test the hypothesis that older women with higher cystatin C are at increased risk of hip fracture independent of traditional risk factors including hip bone mineral density (BMD), we performed a case-cohort analysis nested in a cohort of 4709 white women attending a Year 10 (1997-1998) examination of the Study of Osteoporotic Fractures that included a random sample of 1170 women and the first 300 women with incident hip fracture occurring after Year 10 examination. Serum cystatin C and creatinine were measured in Year 10 sera. In a model adjusted for age, clinical site, body mass index, and total hip BMD, higher cystatin C was associated with an increased risk of hip fracture (p for linear trend 0.008) with women in quartile 4 having a 1.9-fold higher risk (hazard ratio [HR] 1.91; 95% confidence interval [CI], 1.24-2.95) compared with those in quartile 1 (referent group). Further adjustment for additional risk factors only slightly attenuated the association; the risk for hip fracture was 1.7-fold higher (HR 1.74; 95% CI, 1.11-2.72) in women in quartile 4 compared with those in quartile 1. In contrast, neither serum creatinine nor creatinine-based estimated glomerular filtration rate (eGFRCr ) were associated with risk of hip fracture. Older women with higher cystatin C, but not higher serum creatinine or lower eGFRCr , have an increased risk of hip fracture independent of traditional risk factors. These findings suggest that cystatin C may be a promising biomarker for identification of older adults at high risk of hip fracture.

Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures.

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

Twenty-year depressive trajectories among older women.

CONTEXT: Despite the frequent occurrence of depressive symptoms among older adults, especially women, little is known about the long-term course of late-life depressive symptoms. OBJECTIVE: To characterize the natural course of depressive symptoms among older women (from the young old to the oldest old) followed up for almost 20 years. DESIGN: Using latent-class growth-curve analysis, we analyzed women enrolled in an ongoing prospective cohort study (1988 through 2009). SETTING: Clinic sites in Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley near Pittsburgh, Pennsylvania; and Portland, Oregon. PARTICIPANTS: We studied 7240 community-dwelling women 65 years or older. MAIN OUTCOME MEASURE: The Geriatric Depression Scale short form (score range, 0-15) was used to routinely assess depressive symptoms during the follow-up period. RESULTS: Among older women, we identified 4 latent classes during 20 years, with the predicted probabilities of group membership totaling 27.8% with minimal depressive symptoms, 54.0% with persistently low depressive symptoms, 14.8% with increasing depressive symptoms, and 3.4% with persistently high depressive symptoms. In an adjusted model for latent class membership, odds ratios (ORs) for belonging in the increasing depressive symptoms and persistently high depressive symptoms classes, respectively, compared with a group having minimal depressive symptoms were substantially and significantly (P < .05) elevated for the following variables: baseline smoking (ORs, 4.69 and 7.97), physical inactivity (ORs, 2.11 and 2.78), small social network (ORs, 3.24 and 6.75), physical impairment (ORs, 8.11 and 16.43), myocardial infarction (ORs, 2.09 and 2.41), diabetes mellitus (ORs, 2.98 and 3.03), and obesity (ORs, 1.86 and 2.90). CONCLUSIONS: During 20 years, almost 20% of older women experienced persistently high depressive symptoms or increasing depressive symptoms. In addition, these women had more comorbidities, physical impairment, and negative lifestyle factors at baseline. These associations support the need for intervention and prevention strategies to reduce depressive symptoms into the oldest-old years.

Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women.

OBJECTIVE: Previous cross-sectional studies have observed alterations in activity rhythms in dementia patients but the direction of causation is unclear. We determined whether circadian activity rhythms measured in community-dwelling older women are prospectively associated with incident dementia or mild cognitive impairment (MCI). METHODS: Activity rhythm data were collected from 1,282 healthy community-dwelling women from the Study of Osteoporotic Fractures (SOF) cohort (mean age 83 years) with wrist actigraphy for a minimum of three 24-hour periods. Each participant completed a neuropsychological test battery and had clinical cognitive status (dementia, MCI, normal) adjudicated by an expert panel approximately 5 years later. All analyses were adjusted for demographics, body mass index (BMI), functional status, depression, medications, alcohol, caffeine, smoking, health status, and comorbidities. RESULTS: After 4.9 years of follow-up, 195 (15%) women had developed dementia and 302 (24%) had developed MCI. Older women with decreased activity rhythms had a higher likelihood of developing dementia or MCI when comparing those in the lowest quartiles of amplitude (odds ratio [OR] = 1.57; 95% CI, 1.09-2.25) or rhythm robustness (OR = 1.57; 95% CI, 1.10-2.26) to women in the highest quartiles. An increased risk of dementia or MCI (OR = 1.83; 95% CI, 1.29-2.61) was found for women whose timing of peak activity occurred later in the day (after 3:51 PM) when compared to those with average timing (1:34 PM-3:51 PM). INTERPRETATION: Older, healthy women with decreased circadian activity rhythm amplitude and robustness, and delayed rhythms have increased odds of developing dementia and MCI. If confirmed, future studies should examine whether interventions (physical activity, bright light exposure) that influence activity rhythms will reduce the risk of cognitive deterioration in the elderly.

Circulating 25-hydroxyvitamin D levels and frailty status in older women.

CONTEXT: Vitamin D deficiency and frailty are common with aging, but the association between these conditions is uncertain. OBJECTIVE: To determine the association between 25-hydroxyvitamin D (25(OH)D) levels and prevalent and incident frailty status among older women. DESIGN: Cross-sectional and longitudinal analyses of a prospective cohort study. SETTING: Four U.S. centers. PARTICIPANTS: 6307 women aged≥69 years. MAIN OUTCOME MEASURES: Frailty status classified as robust, intermediate stage, or frail at baseline; and robust, intermediate stage, frail, or dead (all-cause mortality) at follow-up an average of 4.5 years later. RESULTS: At baseline, there was a U-shaped association between 25(OH)D level and odds of frailty with the lowest risk among women with levels 20.0-29.9 ng/ml (referent group). Compared with this group, the odds of frailty were higher among those with levels<15.0 ng/ml [multivariable odds ratio (MOR) 1.47, 95% confidence interval (CI), 1.19-1.82], those with levels 15.0-19.9 ng/ml (MOR 1.24, 95% CI 0.99-1.54), and those with levels≥30 ng/ml (MOR 1.32, 95% CI 1.06-1.63). Among 4551 nonfrail women at baseline, the odds of frailty/death (vs. robust/intermediate) at follow-up appeared higher among those with levels 15.0-19.9 ng/ml (MOR 1.21, 95% CI 0.99-1.49), but the CI overlapped 1.0. The odds of death (vs. robust/intermediate/frail at follow-up) was higher among those with levels<15.0 ng/ml (MOR 1.40, 95% CI 1.04-1.88) and those with levels 15.0-19.9 ng/ml (MOR 1.30, 95% CI 0.97-1.75), although the latter association did not quite reach significance. CONCLUSION: Lower (<20 ng/ml) and higher (≥30 ng/ml) levels of 25(OH)D among older women were moderately associated with a higher odds of frailty at baseline. Among nonfrail women at baseline, lower levels (<20 ng/ml) were modestly associated with an increased risk of incident frailty or death at follow-up.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study.

BACKGROUND: Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. OBJECTIVE: We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. DESIGN: We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. RESULTS: Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. CONCLUSIONS: In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

Circadian activity rhythms and mortality: the study of osteoporotic fractures.

OBJECTIVES: To determine whether circadian activity rhythms are associated with mortality in community-dwelling older women. DESIGN: Prospective study of mortality. SETTING: A cohort study of health and aging. PARTICIPANTS: Three thousand twenty-seven community-dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84). MEASUREMENTS: Activity data were collected using wrist actigraphy for a minimum of three 24-hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained. RESULTS: Over an average of 4.1 years of follow-up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all-cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63-2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self-reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29-2.27) and rhythm robustness (HR=1.97, 95% CI=1.50-2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04-4.22) and stroke (HR=2.64, 95% CI=1.11-6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50-4:33 p.m.). CONCLUSION: Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.