Michelle A. Williams

Recreational Physical Activity During Pregnancy and Risk of Preeclampsia

Abstract— The potential benefits and risks of physical activity before and during pregnancy are not well studied. We studied the relation between recreational physical activity and the risk of preeclampsia in a case‐control study of 201 preeclamptic and 383 normotensive pregnant women. Participants provided information about the type, intensity, frequency, and duration of physical activity performed during the first 20 weeks of pregnancy and during the year before pregnancy. Women who engaged in any regular physical activity during early pregnancy, compared with inactive women, experienced a 35% reduced risk of preeclampsia (odds ratio, 0.65; 95% confidence interval [CI], 0.43 to 0.99). Compared with inactive women, those engaged in light or moderate activities (ie, activities with metabolic‐equivalent scores <6) experienced a 24% reduced risk of preeclampsia (95% CI, 0.48 to 1.20). The corresponding reduction for women participating in vigorous activities (metabolic equivalent scores >=6) was 54% (95% CI, 0.27 to 0.79). Brisk walking (average walking pace >=3 mi/h), when compared with no walking at all, was associated with a 30% to 33% reduction in preeclampsia risk. Stair climbing was inversely associated with the risk of preeclampsia (P for trend=0.039). Recreational physical activity performed during the year before pregnancy was associated with similar reductions in preeclampsia risk. These data suggest that regular physical activity, particularly when performed during the year before pregnancy and during early pregnancy, is associated with a reduced risk of preeclampsia.

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus

Background Evidence is accumulating for a role of vitamin D in maintaining normal glucose homeostasis. However, studies that prospectively examined circulating concentrations of 25-hydroxyvitamin D (25-[OH] D) in relation to diabetes risk are limited. Our objective is to determine the association between maternal plasma 25-[OH] D concentrations in early pregnancy and the risk for gestational diabetes mellitus (GDM). Methods A nested case-control study was conducted among a prospective cohort of 953 pregnant women. Among them, 57 incident GDM cases were ascertained and 114 women who were not diagnosed with GDM were selected as controls. Controls were frequency matched to cases for the estimated season of conception of the index pregnancy. Results Among women who developed GDM, maternal plasma 25-[OH] D concentrations at an average of 16 weeks of gestation were significantly lower than controls (24.2 vs. 30.1 ng/ml, P<0.001). This difference remained significant (3.62 ng/ml lower on average in GDM cases than controls (P value = 0.018)) after the adjustment for maternal age, race, family history of diabetes, and pre-pregnancy BMI. Approximately 33% of GDM cases, compared with 14% of controls (P<0.001), had maternal plasma 25-[OH] D concentrations consistent with a pre-specified diagnosis of vitamin D deficiency (<20 ng/ml). After adjustment for the aforementioned covariates including BMI, vitamin D deficiency was associated with a 2.66-fold (OR (95% CI): 2.66 (1.01–7.02)) increased GDM risk. Moreover, each 5 ng/ml decrease in 25-[OH] D concentrations was related to a 1.29-fold increase in GDM risk (OR (95% CI): 1.29 (1.05–1.60)). Additional adjustment for season and physical activity did not change findings substantially. Conclusions Findings from the present study suggest that maternal vitamin D deficiency in early pregnancy is significantly associated with an elevated risk for GDM.

The PhenX Toolkit: Get the Most From Your Measures

The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions.

Perinatal factors and risk of breast cancer

A high level of endogenous estrogen in utero has been hypothesized to he a possible risk factor for breast cancer. We used information from two population-hosed case-control studies to investigate the relation between perinatal factors and risk of invasive breast cancer among women age 21–45 years (746 cases, 960 controls) and women age 50–64 years (401 cases, 439 controls). Breast cancer cases were ascertained through a population-based cancer registry, and controls were selected by random digit dialing. After adjustment for age, menopausal status, and maternal smoking, the birthweight-breast cancer association in women age 21–45 years followed a J-shaped curve, with women whose birthweight was less than 2,500 gm [odds ratio (OR) = 1.3; 95.4, confidence interval (CI) = 09–2.01 and 4,000 gm or more (OR = 1.7; 95% CI = 1.1–2.5) at increased risk. Women age 50–64 years who were 4,000 gm or more at birth appeared to be at slightly reduced risk of breast cancer (OR = 0.6; 95% CI = 0.3–1.1). With the exception of maternal smirking, there was little effect of other perinatal factors on breast cancer risk in either group. These results support the hypothesized association between intrauterine estrogen exposure and subsequent risk of breast cancer.

Pracental abruption and its association with hypertension and prolonged rupture of membranes: A methodologic review and meta-analysis*

Objective To conduct a meta-analysis of published studies on placental abruption to examine its incidence, recurrence, and association with hypertensive disorders (chronic hyper-tension and preeclampsia) and prolonged rupture of membranes (PROM) in pregnancy. Data Sources We reviewed studies on placental abruption published since 1950, based on a comprehensive literature search using MEDLINE, and by identifying studies cited in the references of published reports. Methods of Study Selection We identified 54 studies, excluding case reports on placental abruption and studies relating to placenta previa and vaginal bleeding of unknown origin. We also restricted the search to articles published in English. Tabulation, Integration, and Results Studies chosen for the meta-analysis were categorized based on their study design (case-control or cohort), where they were conducted (United States or other countries), source of the data (vital records versus other sources), and magnitude of risk (risk of abruption greater or less than 1.0%). We used both fixed- and random-effects analysis to identify sources of heterogeneity in results among studies. There were striking differences in the incidence of placental abruption between cohort (0.69%) and case-control (0.35%) studies. United States-based studies found a somewhat higher incidence both for cohort (0.81%) and case-control (0.37%) studies compared with studies conducted outside the U.S. (0.60% and 0.26%, respectively). Abruption was more than ten times more common in pregnancies preceded by a pregnancy with abruption. Chronically hypertensive patients were more than three times as likely to develop placental abruption (odds ratio [OR] 3.13, 95% confidence interval [CI] 2.04–4.80) as normotensive patients. The OR for placental abruption was 1.73 (95% CI 1.47–2.04) for patients with preeclampsia. Similarly, women with pregnancies complicated by PROM were more than three times as likely to develop placental abruption (OR 3.05, 95% CI 2.16–4.32). United States-based studies, case-control studies, and studies with an incidence of abruption greater than 1% demonstrated stronger associations between abruption and hypertension and PROM. Conclusion Risk of abruption is strongly associated with chronic hypertension, PROM, and especially abruption in a prior pregnancy, and somewhat more modestly with pre-eclampsia. The criteria for the diagnosis of placental abruption, hypertensive disorders, and PROM may have introduced variability among the results of these studies. More standardized definitions of these pregnancy complications would improve the comparability of the study results.

The frequency of breech presentation by gestational age at birth: A large population-based study

From a study of birth records, breech presentation at delivery for each gestational age was found to be less frequent as compared with other reports about antenatal ultrasonographic examination. Selection bias or the effect of labor may account for the observed difference.

Placental microRNA expression in pregnancies complicated by preeclampsia

OBJECTIVE The role of posttranscription regulation in preeclampsia is largely unknown. We investigated preeclampsia-related placental microRNA (miRNA) expression using microarray and confirmatory quantitative real-time polymerase chain reaction experiments. STUDY DESIGN Placental expressions of characterized and novel miRNAs (1295 probes) were measured in samples collected from 20 preeclampsia cases and 20 controls. Differential expression was evaluated using Student t test and fold change analyses. In pathway analysis, we examined functions/functional relationships of targets of differentially expressed miRNAs. RESULTS Eight miRNAs were differentially expressed (1 up-regulated and 7 down-regulated) among preeclampsia cases compared with controls. These included previously identified candidates (miR-210, miR-1, and a miRNA in the 14q32.31 cluster region) and others that are novel (miR-584 and miR-34c-5p). These miRNAs target genes that participate in organ/system development (cardiovascular and reproductive system), immunologic dysfunction, cell adhesion, cell cycle, and signaling. CONCLUSION Expression of miRNAs that target genes in diverse pathophysiological processes is altered in the setting of preeclampsia.

Avoiding serious infections associated with abdominal hysterectomy: A meta-analysis of antibiotic prophylaxis

OBJECTIVE Our objective was to determine whether the use of preoperative antibiotics prevents serious infections associated with total abdominal hysterectomy. STUDY DESIGN We identified 25 randomized controlled trials of antibiotic prophylaxis that used rigorous protocols. We performed meta-analysis and cumulative meta-analyses for all of the trials, and then we performed separate meta-analysis for cefazolin, metronidazole, and tinidazole. RESULTS Overall, 21.1% (373 of 1768) of the patients who did not receive antibiotic prophylaxis had serious infections after abdominal hysterectomy. Among patients who received any antibiotics, we found that 9.0% (166/1836) had serious postoperative infections; among those who received cefazolin, metronidazole, or tinidazole, 11.4% (70 of 615), 6.3% (17 of 269), and 5.0% (5 of 101), respectively, had serious postoperative morbidity. The differences in the prevalence of infection between women who received prophylaxis and women who did not receive prophylaxis were statistically significant (any antibiotics, p = 0.00001; cefazolin, p = 0.00021; metronidazole, p = 0.015; and tinidazole, p = 0.034). CONCLUSION Because preoperative antibiotics are highly effective in the prevention of serious infections associated with total abdominal hysterectomy, we believe they should be used routinely. In addition, we believe that the use of controls who receive no treatment is no longer justified in trials of antibiotic prophylaxis for total abdominal hysterectomy.

Understanding the biological basis of autofluorescence imaging for oral cancer detection: high-resolution fluorescence microscopy in viable tissue.

Purpose: Autofluorescence imaging is increasingly used to noninvasively identify neoplastic oral cavity lesions. Improving the diagnostic accuracy of these techniques requires a better understanding of the biological basis for optical changes associated with neoplastic transformation in oral tissue. Experimental Design: A total of 49 oral biopsies were considered in this study. The autofluorescence patterns of viable normal, benign, and neoplastic oral tissue were imaged using high-resolution confocal fluorescence microscopy. Results: The autofluorescence properties of oral tissue vary significantly based on anatomic site and pathologic diagnosis. In normal oral tissue, most of the epithelial autofluorescence originates from the cytoplasm of cells in the basal and intermediate regions, whereas structural fibers are responsible for most of the stromal fluorescence. A strongly fluorescent superficial layer was observed in tissues from the palate and the gingiva, which contrasts with the weakly fluorescent superficial layer found in other oral sites. Upon UV excitation, benign inflammation shows decreased epithelial fluorescence, whereas dysplasia displays increased epithelial fluorescence compared with normal oral tissue. Stromal fluorescence in both benign inflammation and dysplasia drops significantly at UV and 488 nm excitation. Conclusion: Imaging oral lesions with optical devices/probes that sample mostly stromal fluorescence may result in a similar loss of fluorescence intensity and may fail to distinguish benign from precancerous lesions. Improved diagnostic accuracy may be achieved by designing optical probes/devices that distinguish epithelial fluorescence from stromal fluorescence and by using excitation wavelengths in the UV range.

Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson cancer center

Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities.