Utility of Population Attributable Fraction Assessment in Guiding Interventions to Reduce Low Birthweight in the High-Altitude State of Colorado.

Objectives We evaluated the ability of population attributable fraction (PAF) assessments to alter significant modifiable risks for low birthweight (LBW) and the impact of high altitude as a risk for LBW in Colorado. Methods Logistic regression analysis of birth certificate parameters in 1995-1997 identified risk factors for PAF assessment. PAF for birth at high altitude, multiple births, and LBW in singleton births were determined. Subsequent analysis of singleton LBW risks, using number needed to treat (NNT) analysis, estimated how elimination of major modifiable risk factors could reduce LBW in the study population. Public health interventions were initiated and PAF analysis conducted 12 years afterward to determine the effect of interventions. Results PAF in singleton births revealed low maternal weight gain in pregnancy and maternal smoking as the greatest modifiable attributable risk factors for LBW (12.7/12.5 %, respectively, in 1995-1997 and 12.9/7.1 % in 2007-2009). Significant interaction between these variables resulted in PAF of 34.4 % when the two occurred together in 1995-1997, decreasing to 19.4 % in 2007-2009. NNT analysis of singleton births in 1995-1997 revealed that eliminating low maternal weight gain, smoking, late prenatal care in all women and interpregnancy intervals <1 year in multiparous women reduced LBW by 46.5 %. The respective proportional reductions in PAF of 40.3 and 46.3 % for maternal smoking and weight gain/smoking interaction were associated with a 1.4 % LBW reduction in singleton births between the two study periods. Conclusions for Practice PAF and NNT analyses are valuable tools to predict intervention targets to lower LBW.

The Effect of Omega-3 Docosahexaenoic Acid Supplementation on Gestational Length: Randomized Trial of Supplementation Compared to Nutrition Education for Increasing n-3 Intake from Foods.

OBJECTIVE: DHA supplementation was compared to nutrition education to increase DHA consumption from fish and DHA fortified foods. DESIGN: This two-part intervention included a randomized double-blind placebo controlled DHA supplementation arm and a nutrition education arm designed to increase intake of DHA from dietary sources by 300 mg per day. SETTING: Denver Health Hospitals and Clinics, Denver, Colorado, USA. POPULATION: 871 pregnant women aged 18-40 were recruited between 16 and 20 weeks of gestation of whom 564 completed the study and complete delivery data was available in 505 women and infants. METHODS: Subjects received either 300 or 600 mg DHA or olive oil placebo or nutrition education. MAIN OUTCOME VARIABLE: Gestational length. RESULTS: Gestational length was significantly increased by 4.0-4.5 days in women supplemented with 600 mg DHA per day or provided with nutrition education. Each 1% increase in RBC DHA at delivery was associated with a 1.6-day increase in gestational length. No significant effects on birth weight, birth length, or head circumference were demonstrated. The rate of early preterm birth (1.7%) in those supplemented with DHA (combined 300 and 600 mg/day) was significantly lower than in controls. CONCLUSION: Nutrition education or supplementation with DHA can be effective in increasing gestational length.

Consensus clinical practice guidelines for the diagnosis and treatment of restless legs syndrome/Willis-Ekbom disease during pregnancy and lactation.

Restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is common during pregnancy, affecting approximately one in five pregnant women in Western countries. Many report moderate or severe symptoms and negative impact on sleep. There is very little information in the medical literature for practitioners on the management of this condition during pregnancy. Accordingly, a task force was chosen by the International RLS Study Group (IRLSSG) to develop guidelines for the diagnosis and treatment of RLS/WED during pregnancy and lactation. A committee of nine experts in RLS/WED and/or obstetrics developed a set of 12 consensus questions, conducted a literature search, and extensively discussed potential guidelines. Recommendations were approved by the IRLSSG executive committee, reviewed by IRLSSG membership, and approved by the WED Foundation Medical Advisory Board. These guidelines address diagnosis, differential diagnosis, clinical course, and severity assessment of RLS/WED during pregnancy and lactation. Nonpharmacologic approaches, including reassurance, exercise and avoidance of exacerbating factors, are outlined. A rationale for iron supplementation is presented. Medications for RLS/WED are risk/benefit rated for use during pregnancy and lactation. A few are rated "may be considered" when RLS/WED is refractory to more conservative approaches. An algorithm summarizes the recommendations. These guidelines are intended to improve clinical practice and promote further research.

Fumonisin mycotoxin contamination of corn-based foods consumed by potentially pregnant women in southern California.

OBJECTIVE: To evaluate a sample of locally available corn-based foods for fumonisin contamination. STUDY DESIGN: We analyzed 38 corn tortilla and masa flour samples from Los Angeles, San Diego and Tijuana, Mexico,for fumonisin contamination. Retail sources were diverse and not limited to Hispanic neighborhoods. RESULTS: Fumonisins were found in all samples. The median fumonisin B1 mycotoxin level was 84 ng/g, with a range of 1-729 (n = 38). The median total fumonisin level was 231 ng/g, with a range of 2.8-1,863. Levels of fumonisins differed by geographic site. CONCLUSION: Fumonisin contamination of corn-based foods in southern California is common. At levels of contamination > 1,000 ng/g, a 60-kg potentially pregnant woman could exceed the World Health Organization recommendations by eating 120 g (dry weight) of corn products daily. Fumonisin contamination may constitute a preventable risk for NTDs among susceptible reproductive-age women and their progeny.

Chlamydia heat shock protein 60 induces trophoblast apoptosis through TLR4.

Intrauterine infection affects placental development and function, and subsequently may lead to complications such as preterm delivery, intrauterine growth retardation, and preeclampsia; however, the molecular mechanisms are not clearly known. TLRs mediate innate immune responses in placenta, and recently, TLR2-induced trophoblast apoptosis has been suggested to play a role in infection-induced preterm delivery. Chlamydia trachomatis is the etiological agent of the most prevalent sexually transmitted bacterial infection in the United States. In this study, we show that in vitro chlamydial heat shock protein 60 induces apoptosis in primary human trophoblasts, placental fibroblasts, and the JEG3 trophoblast cell line, and that TLR4 mediates this event. We observed a host cell type-dependent apoptotic response. In primary placental fibroblasts, chlamydial heat shock protein 60-induced apoptosis was caspase dependent, whereas in JEG3 trophoblast cell lines it was caspase independent. These data suggest that TLR4 stimulation induces apoptosis in placenta, and this could provide a novel mechanism of pathogenesis for poor fertility and pregnancy outcome in women with persistent chlamydia infection.

Readily treatable reproductive tract infections and preterm birth among black women.

OBJECTIVE: This study sought to quantify the risks of preterm birth that are ascribable to potentially treatable reproductive tract infections among black women in Denver, Colorado. STUDY DESIGN: A secondary analysis was conducted of 4 prospective studies in Denver, Colorado, that included 1038 women who were enrolled at < 29 weeks of gestation and whose cases were followed through delivery. Rates of preterm birth, preterm labor, and preterm premature rupture of membranes were the primary outcomes that were examined. RESULTS: Bacterial vaginosis, infection with Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma hominis, Neisseria gonorrhoeae, and group B streptococcal colonization were more common among black women (P < .01) than among comparators. Preterm birth occurred more often among black women with infections that were being studied (20.4%), compared with uninfected black women (9.5%; relative risk, 2.2; 95% CI, 1.1-4.1). Up to 42% of preterm births among black women were attributable to the presence of bacterial vaginosis, T vaginalis, or C trachomatis alone or in combinations. The risk for preterm birth among infected black women who received Centers for Disease Control and Prevention recommended treatment was reduced significantly (relative risk, 0.16; 95% CI, 0.04-0.66). CONCLUSION: Black women have increased risks of prematurity that are associated with prevalent reproductive tract infections during pregnancy. Preterm birth among similar urban black women could be reduced by > 40% by the screening and treatment of common genitourinary tract infections in pregnancy.

Mode of delivery is associated with asthma and allergy occurrences in children.

PURPOSE: A growing body of evidence indicates that perinatal factors modulate immune development and thereby may affect childhood asthma risk. In this study, we examined the associations between birth by cesarean section (C-section) and atopic disease occurrence in childhood. METHODS: Subjects were born in California between 1975 and 1987 and were 8 to 17 years old during their enrollment in the Children's Health Study. Our analysis was restricted to 3464 children born at or after 37 weeks of gestation with a birth weight of 2500 g or greater based on birth certificate data. Information about sociodemographic factors, reported physician-diagnosed asthma, and other atopic diseases was obtained by using a self-administered structured questionnaire. Logistic regression models were fitted to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Children born by C-section were at increased risk for asthma (OR, 1.33; 95% CI, 1.01-1.75), hay fever (OR, 1.57; 95% CI, 1.24-1.99), and allergy (OR, 1.26; 95% CI, 1.03-1.53) compared with those born vaginally. Risk associated with C-section was the same for children regardless of family history of asthma or allergy. CONCLUSION: We conclude that birth by C-section or processes associated with it may increase the risk for atopic disease in childhood.

Douching, pelvic inflammatory disease, and incident gonococcal and chlamydial genital infection in a cohort of high-risk women.

Douching has been linked to gonococcal or chlamydial cervicitis and pelvic inflammatory disease (PID) in retrospective studies. The authors conducted a 1999-2004 prospective observational study of 1,199 US women who were at high risk of acquiring chlamydia and were followed for up to 4 years. Cervical Neisseria gonorrhoeae and Chlamydia trachomatis were detected from vaginal swabs by nucleic acid amplification. PID was characterized by histologic endometritis or pelvic pain and tenderness plus one of the following: oral temperature >38.3 degrees C, leukorrhea or mucopus, erythrocyte sedimentation rate >15 mm/hour, white blood cell count >10,000, or gonococcal/chlamydial lower genital tract infection. Associations between douching and PID or gonococcal/chlamydial genital infections were assessed by proportional hazards models. The 4-year incidence rate of PID was 10.9% and of gonococcal and/or chlamydial cervicitis was 21.9%. After adjustment for confounding factors, douching two or more times per month at baseline was associated with neither PID (adjusted hazard ratio = 0.76, 95% confidence interval: 0.42, 1.38) nor gonococcal/chlamydial genital infection (adjusted hazard ratio = 1.16, 95% confidence interval: 0.76, 1.78). Frequency of douching immediately preceding PID or gonococcal/chlamydial genital infection was not different between women who developed versus did not develop outcomes. These data do not support an association between douching and development of PID or gonococcal/chlamydial genital infection among predominantly young, African-American women.

Bacterial vaginosis and risk of pelvic inflammatory disease.

BACKGROUND: Bacterial vaginosis commonly is found in women with pelvic inflammatory disease (PID), but it is unclear whether bacterial vaginosis leads to incident PID. METHODS: Women (n = 1,179) from 5 U.S. centers were evaluated for a median of 3 years. Every 6-12 months, vaginal swabs were obtained for gram stain and culture of microflora. A vaginal microflora gram stain score of 7-10 was categorized as bacterial vaginosis. Pelvic inflammatory disease was diagnosed by presence of either histologic endometritis or pelvic pain and tenderness plus one of the following: oral temperature greater than 38.3 degrees C; sedimentation rate greater than 15 mm/hour; white blood count greater than 10,000; or lower genital tract detection of leukorrhea, mucopus, or Neisseria gonorrhoeae or Chlamydia trachomatis. RESULTS: After adjustment for relevant demographic and lifestyle factors, baseline bacterial vaginosis was not associated with the development of PID (adjusted hazard ratio 0.89, 95% confidence interval 0.55-1.45). Carriage of bacterial vaginosis in the previous 6 months before a diagnosis (adjusted risk ratio 1.31, 95% confidence interval 0.71-2.42) also was not significantly associated with PID. Similarly, neither absence of hydrogen peroxide-producing Lactobacillus nor high levels of Gardnerella vaginalis significantly increased the risk of PID. Dense growth of pigmented, anaerobic gram-negative rods in the 6 months before diagnosis did significantly increase a woman's risk of PID (P =.04). One subgroup of women, women with 2 or more recent sexual partners, demonstrated associations among bacterial vaginosis, Gardnerella vaginalis, anaerobic gram-negative rods, and PID. CONCLUSION: In this cohort of high-risk women, after adjustment for confounding factors, we found no overall increased risk of developing incident PID among women with bacterial vaginosis. LEVEL OF EVIDENCE: II-2

Immunohistochemical localization of the IAP protein survivin in bladder mucosa and transitional cell carcinoma.

In the current study, the immunohistochemical localization of survivin was correlated with the histologic diagnosis in healthy transitional cell epithelium, transitional cell carcinoma (TCC) in situ, and TCC of the urinary bladder. Forty-five TCCs (grades 1-3, 15 of each), 14 cases of TCC in situ, and II healthy bladder mucosal specimens were selected from archival collections of formalin-fixed bladder tissues. Slides were reacted with an anti-survivin antibody using a conventional immunohistochemical method and then were scored for nuclear and cytoplasmic staining. Statistical analysis of survivin expression was performed to evaluate the correlation of staining pattern with histologic diagnosis and clinical outcome. Nuclear staining for survivin was detected in 26 of 45 TCCs and in 2 of 14 cases of TCC in situ, but was not detected in healthy bladder mucosa. The association of nuclear staining with TCC versus both healthy bladder mucosa and TCC in situ was statistically significant (P < 0.001). Patients with TCC and a nuclear pattern of survivin localization had a greater period of disease-free survival (27.2 months) than was observed in patients with TCC that showed no nuclear staining for survivin (9.9 months); however, the differences were not statistically significant. Nuclear localization of survivin is a marker of TCC but is rarely present in premalignant or benign bladder mucosal specimens.

Does incomplete growth and development predispose teenagers to preterm delivery? A template for research.

Pregnant teenagers are in better physical condition, suffer from fewer chronic diseases, and engage in fewer health-risky behaviors than socioeconomically similar pregnant adults, but give birth to a disproportionately large number of preterm infants. This systematic review of the adolescent pregnancy literature defines the unique risks associated with being young and pregnant by examining how the physical and psychosocial changes that are characteristic of puberty and adolescence interact with traditional risk factors for preterm delivery. The need for age-specific interventions is discussed and recommendations for future research are made.

Correlation of survivin mRNA detection with histologic diagnosis in normal endometrium and endometrial carcinoma.

BACKGROUND: The objective of this study was to determine if survivin mRNA expression is a marker of endometrioid adenocarcinoma and if survivin mRNA levels correlate with tumor grade and stage. METHODS: Twenty-six samples of endometrioid adenocarcinoma and 18 cases of benign endometrium were obtained at surgery. RNA was extracted from tissues and was used for quantitative real-time RT-PCR, targeting a 91-bp sequence of survivin mRNA and the levels were standardized to the levels of ribosomal RNA. Statistical analysis of the correlation between histologic diagnosis and the corrected survivin mRNA levels was performed by the Fisher Exact test and the Kruskal-Wallis test. RESULTS: Survivin mRNA was detected in all specimens. Survivin mRNA levels were increased in proliferative endometrium (P = 0.0509) and was increased in correlation with ascending grade in endometrioid adenocarcinoma (P = 0.01). CONCLUSION: Survivin mRNA is not a specific marker of endometrial cancer, but may reflect an important mechanism in tumor progression of the endometrial mucosa.

Quantitative analysis of telomerase hTERT mRNA and telomerase activity in endometrioid adenocarcinoma and in normal endometrium.

OBJECTIVES: In the current study, the quantitative levels of telomerase hTERT mRNA and the functional telomerase repeat amplification protocol (TRAP) assay were correlated with tumor grade in endometrial carcinomas and with the histologic phase of normal endometrium. METHODS: Twenty-six samples of endometroid adenocarcinoma and 20 cases of benign endometrium were obtained from hysterectomy specimens. Total RNA was extracted from each tissue sample and used for quantitative real-time RT-PCR of hTERT mRNA and the levels were standardized to the levels of ribosomal RNA. Quantitative determination of telomerase activity was performed by the polymerase chain-based TRAP assay and the levels of expression were defined by the ratio of radioactivity incorporated into the 6-bp telomerase amplification products versus the radioactivity incorporated into an internal standard (telomerase/ITAS x 100 = 1 RU). Statistical analyses were performed using the Fisher exact test or chi2 test, a Wilcoxon rank sum test, and a linear regression analysis. RESULTS: hTERT mRNA and telomerase activity levels showed a linear association in the study group (P = 0.006, R2 = 0.139). hTERT mRNA levels and telomerase activity levels were significantly higher in endometrial cancer (179 pg/ng rRNA, 44 relative units (RU)) than in normal endometrium (45 pg/ng), (15 RU) (P = 0.009, P = 0.006). In normal endometrium, hTERT mRNA and telomerase activity levels were highest in the proliferative phase (74 pg/ng rRNA, 25 RU) and were relatively low in secretory (13 pg/ng rRNA, 6 RU) and atrophic endometrium (9 pg/ng rRNA, 2 RU). CONCLUSION: These results suggest that the quantitative analysis of hTERT and telomerase activity may have potential roles as diagnostic or prognostic adjuncts for both premenopausal and postmenopausal patients with endometrial cancer.