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A total of 403 women (aged 14-25 years) were surveyed to determine the association of psychosocial variables with risky sexual behaviors and sexually transmitted infections (STIs). Depression, stress, and low social support were associated with high-risk sexual behaviors and past STIs. When comparing adolescent women (aged 14-19) to young women (aged 20-25), the adolescents had stronger associations with the outcome variables.

The objective was to assess the independent effect of regular periconceptional multivitamin use on the risk of preeclampsia. Pregnant women (n=1,835) enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001) at less than 16 weeks' gestation were asked whether they regularly used multivitamins or prenatal vitamins in the past 6 months. Women were classified as users or nonusers. The unadjusted prevalence of preeclampsia was 4.4% in nonusers and 3.8% in users. After adjustment for race/ethnicity, marital status, parity, prepregnancy physical activity, and income in a multiple logistic regression model, regular use of multivitamins was associated with a 45% reduction in preeclampsia risk compared with nonuse (odds ratio (OR)=0.55, 95% confidence interval (CI): 0.32, 0.95). Prepregnancy overweight modified this effect. After confounder adjustment, lean multivitamin users had a 71% reduction in preeclampsia risk compared with lean nonusers (OR=0.29, 95% CI: 0.12, 0.65). In contrast, there was no relation between multivitamin use and preeclampsia among overweight women (OR=1.08, 95% CI: 0.52, 2.25). A sensitivity analysis for unmeasured confounding by fruit and vegetable intake supported these conclusions. If confirmed by others, these results suggest that regular use of a multivitamin supplement in the periconceptional period may help to prevent preeclampsia, particularly among lean women.

Background: Chlorhexidine (CHX) digluconate exerts plaque inhibitory efficacy in the natural dentition environment due to a superior degree of persistence at the tooth surface. The purpose of the present study was to assess the interaction of CHX with titanium surfaces to estimate its antiplaque potential in the peri-implant environment., Methods: Saliva-coated machined smooth (S) and sand-blasted acid-etched rough (R) titanium disks were soaked in either 0.1% or 0.2% CHX solution. After 24 hours, CHX amounts that were adsorbed, washed out, and desorbed from the titanium surfaces were determined spectrophotometrically at 230 nm. The antibacterial activity of CHX-treated titanium disks was assessed by measuring bacterial inhibition zones on Streptococcus mutans lawns., Results: Titanium disks adsorbed 3% to 8% of the available CHX, which was significantly higher with 0.2% CHX (P<0.001) than with 0.1% CHX and two-fold higher on the R titanium disks compared to S titanium surface (P<0.001). After rinsing with water, 2.2% of the adsorbed CHX was washed out. Over 24 hours, S- and R-type disks released 1.1% and 0.6% of the adsorbed agent, respectively. Larger bacterial inhibition zones were obtained with 0.2% CHX and in R disks compared to S disks., Conclusions: CHX displayed persistence at the titanium surface. The adsorption level and bacterial growth inhibition were affected by CHX concentration and titanium surface characteristics, with higher levels of adsorption and antibacterial activity with 0.2% CHX and rough titanium surface. The slow CHX release rate suggests persistence of this agent at the titanium-pellicle surface, which can provide a long-term antiplaque effect.

Intrauterine growth restriction (IUGR) and preeclampsia differ in their association with maternal disease but share a similar placental pathology. Moreover, mothers who have had pregnancies complicated by preeclampsia or IUGR are at elevated later-life cardiovascular risk. Why, then, do some women develop IUGR and others develop preeclampsia? In this clinical opinion, based on a review of the literature, we hypothesize that both women experiencing preeclampsia and IUGR enter pregnancy with some degree of endothelial dysfunction, a lesion that predisposes to shallow placentation. In our opinion, preeclampsia develops when abnormal placentation, through the mediator of elevated circulating cytokines, interacts with maternal metabolic syndrome, comprised of adiposity, insulin resistance/hyperglycemia, hyperlipidemia, and coagulopathy. IUGR develops in the absence of antenatal metabolic syndrome. Among these women, the baby is affected by shallow placentation but the mother does not develop clinically apparent disease. This conceptualization provides a testable framework for future etiologic studies of preeclampsia and IUGR.

Objectives: To examine variability in bacterial vaginosis (BV) over 6- to 12-month intervals., Study Design: One thousand one hundred ninety-three women were followed for a median of 3 years with serial vaginal swab Gram stains for BV. Discrete time hazard models were fit to identify independent risk factors for BV., Results: Women with BV at study entry were categorized as having normal flora at the next visit 20% of the time, and women with normal flora at study entry were categorized as having BV at the next visit 20% of the time. Among women with initially normal flora, factors associated with BV were black race, lower education, a history of BV, a history of chlamydial/gonococcal cervicitis, and lack of monogamy., Conclusion: About one fifth of women with normal flora develop BV over a given 6- to 12-month interval, and the modifiable risk factors of cervicitis and lack of monogamy contribute to the development of BV.

Objective: A single live birth compared to nulliparity significantly reduces the risk for ovarian cancer, but exactly how pregnancy reduces ovarian cancer risk is unknown. We sought to determine whether offspring gender, which differentially alters maternal hormonal milieu, may be associated with maternal ovarian cancer risk., Methods: Parous women (n = 511) with incident ovarian cancer were compared to parous community controls (n = 1136) participating in a population-based case-control study of ovarian cancer (Delaware Valley, 1994-1998). In subgroup specific models for women with one, two, or three births, multivariate logistic regression was used to assess the relationship between ovarian cancer and offspring gender, adjusting for age, race, education, oral contraceptives, breast feeding, tubal ligation, and ovarian cancer family history., Results: Compared to having all girls, women with all boys tended to have a reduced risk of ovarian cancer (OR = 0.80 95% CI: 0.58, 1.10), while women with boys and girls conferred the greatest protection (OR = 0.58, 95% CI: 0.43, 0.79). Among women with two births, the association was observed for those with one boy and one girl (OR = 0.63, 95% CI: 0.40, 1.00), but not for those with two male offspring (OR = 1.12, 95% CI: 0.68, 1.85). This result was consistent among women with three births (OR = 0.42, 95% CI: 0.21, 0.84; OR = 0.47, 95% CI: 0.23, 0.95; OR = 0.49, 95% CI: 0.20, 1.21; for one, two, and three boys, respectively, compared to all girls)., Conclusion: Compared to having all girls, bearing both male and female offspring may be associated with a decrease in maternal ovarian cancer risk, although the biologic relevance of this observation is unclear.

Purpose: Little is known about how physicians' attitudes and knowledge of contraception could impact the unintended pregnancy rate in the United States. The objective of this study was to analyze survey data from physicians in primary care training programs in Pittsburgh, PA., Methods: A cross-sectional survey was administered to primary care medical residents in Allegheny County, PA. Descriptive statistics were used to illustrate training, attitudes and knowledge regarding contraceptive management. A multivariable analysis was performed to elucidate associations between training, attitudes and behavior., Results: Of 143 residents surveyed, 74 (52%) responded. The mean score on contraceptive knowledge assessment was 54%. Obstetrics/gynecology residents performed consistently better on the knowledge index (p<.01). Among nonobstetrics/gynecology residents, formal training in contraception, female gender, ability to insert an intrauterine device and not being a family practitioner were independently associated with improved knowledge (p<.05)., Conclusions: Most of the responding graduating residents view contraception as an important component of primary care. However, young physicians have a contraceptive knowledge base that is inconsistent across primary care specialties. Improvement in this area might improve the unintended pregnancy rate in the United States.

Purpose: We assessed the accuracy and reliability of maternal recall of infant birth weight 35 to 70 years after delivery., Methods: A total of 120 well functioning women (mean age 80 years; 45% Black) reported the birth weight for each live birth and then provided documentation of birth weights (n = 22) or reported birth weights a second time (n = 98)., Results: Agreement between recalled and documented birth weights was high for first births (ICC = 0.96) but moderate for subsequent births (ICC = 0.59). Maternal recall was highly reliable for first births (r = 0.95) and subsequent births (r = 0.87), and reliability remained high when considered separately by race, education, income, and age., Conclusion: Women report accurate and reliable infant birth-weight data an average of 57 years after delivery, and recall is particularly precise for first births.

Background: The association between anthropometric factors and ovarian cancer risk was investigated using data from 762 cases and 1348 controls participating in a population-based case-control study in the Delaware Valley from 1994-1998. Because factors such as oral contraceptive (OC), hormone therapy (HT), and parity may affect weight and hormone levels, the associations were examined in women with and without these characteristics., Methods: Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals while controlling for age, race, parity, family history of ovarian cancer, tubal ligation, and OC use., Results: Compared with controls, cases were taller and heavier in recent years and at age 18. Results did not differ by OC or HT use. However, anthropometric associations differed significantly based on parity, as increasing anthropometric measures were associated with increased ovarian cancer risk among nulliparous women only. Adjusted OR for recent body mass index (BMI) quartile 4 compared with quartile 1 for nulliparous women was 2.53 (95% confidence interval [CI]: 1.39, 4.61) compared with 0.96 (95% CI: 0.70, 1.31) for parous women. Additionally, adult weight gain was significant only for nulliparous women. Adjusted OR for weight change (recent to age 18) quartile 4 compared with quartile 1 for nulliparous women was 3.73 (95% CI: 1.88, 7.42) versus 1.09 (95% CI: 0.78, 1.51) for parous women., Conclusions: BMI and weight in women's adult lifetime may be positively associated with ovarian cancer risk. Observations were most apparent for nulliparous women, possibly reflecting an interaction between local inflammation caused by incessant ovulation and increased estrogen exposure on ovarian epithelium., (Copyright 2006 American Cancer Society)

Background: Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70., Methods: Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70-92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density., Results: Median (range) percent density among women was 23.7% (0-85%). Body mass index (beta=-0.345, p<0.001 adjusted for age and parity) and parity (beta=-0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (beta=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (beta=-0.35), parity (beta=-0.29), surgical menopause (beta=0.13) and current smoking (beta=-0.12)., Conclusion: Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.

Chronic inflammation has been implicated in a variety of cancers. In this review, we consider associations between endometriosis and cancers both local (ovarian) and distant (breast). We review the epidemiological data linking endometriosis to ovarian and breast cancers. We then consider evidence for a role for sex steroid hormones and for inflammation in the aetiology of each of these cancers. Finally, we consider that endometriosis may promote alterations in sex steroid hormones and inflammatory mediators. A possible explanation for the association between endometriosis and these reproductive cancers may then be local and systemic enhancement of aberrant inflammatory and hormonal mediators. If this hypothesis is true, endometriosis may need to be considered as a risk factor for ovarian and breast cancers, triggering increasingly intensive surveillance. Moreover, treatments for endometriosis may require consideration of the impact on long-term cancer risk.

Pelvic inflammatory disease, the infection and inflammation of the female upper genital tract, is a common cause of infertility, chronic pain and ectopic pregnancy. Diagnosis and management are challenging, due largely to a polymicrobial etiology which is not fully delineated. Signs and symptoms of this syndrome vary widely, further complicating diagnosis and treatment. Due to the potential for serious sequelae, a low threshold for diagnosis and treatment is recommended. Since pelvic inflammatory disease has a multimicrobial etiology including Neisseria gonorrhoeae, Chlamydia trachomatis and anaerobic and mycoplasmal bacteria, treatment of pelvic inflammatory disease should be broad spectrum. Recent treatment trials have focused on shorter duration regimens such as azithromycin and monotherapies including ofloxacin, although data are sparse. Research comparing sequelae development by differing antimicrobial regimens is extremely limited, but will ultimately shape future treatment guidelines. Several promising short-duration and monotherapy antibiotic regimens should be evaluated in pelvic inflammatory disease treatment trials for compliance, microbiological and clinical cure, and reduction of subsequent adverse reproductive and gynecological morbidity.

Objectives: To assess prediction strategies for pelvic inflammatory disease (PID)., Study Design: One thousand one hundred seventy women were enrolled based on a high chlamydial risk score. Incident PID over a median of 3 years was diagnosed by either histologic endometritis or Centers for Disease Control and Prevention criteria. A multivariable prediction model for PID was assessed., Results: Women enrolled using the risk score were young, single, sexually active, and often had prior sexually transmitted infections. Incident PID was common (8.6%). From 24 potential predictors, significant factors included age at first sex, gonococcal/chlamydial cervicitis, history of PID, family income, smoking, medroxyprogesterone acetate use, and sex with menses. The model correctly predicted 74% of incident PID; in validation models, correct prediction was only 69%., Conclusions: Our data validate a modified chlamydial risk factor scoring system for prediction of PID. Additional multivariable modeling contributed little to prediction. Women identified by a threshold value on the chlamydial risk score should undergo intensive education and screening.

Prenatal exposure to carcinogens results in newborn DNA damage which in turn is associated with impaired health conditions in both childhood and adulthood. The present study aimed to evaluate whether phase I and II biotransformation enzyme genetic polymorphisms in combination with environmental exposures during pregnancy result in elevated levels of newborn DNA damage. Maternal peripheral and umbilical cord blood samples from 406 mother/newborn pairs were genotyped for a panel of phase I/II metabolic enzymes (CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2) responsible for the metabolism of tobacco and lifestyle-related mutagens and carcinogens. DNA damage was measured by somatic cell mutation frequency at the glycophorin A (GPA) locus in newborns. No association with elevated somatic cell mutation frequency was observed between the combination of maternal/newborn genotypes and cigarette smoke or lifestyle exposures. The observed variation in newborn GPA frequency might be due to either environmental factors not assessed in this study or inter-individual differences in alternative metabolic or DNA repair pathways.

Pelvic inflammatory disease (PID) is a frequent condition of young women, often resulting in reproductive morbidity. Although Neisseria gonorrhoeae and/or Chlamydia trachomatis are/is recovered from approximately a third to a half of women with PID, the etiologic agent is often unidentified. We need PCR to test for M genitalium among a pilot sample of 50 women with nongonococcal, nonchlamydial endometritis enrolled in the PID evaluation and clinical health (PEACH) study. All participants had pelvic pain, pelvic organ tenderness, and leukorrhea, mucopurulent cervicitis, or untreated cervicitis. Endometritis was defined as > or =5 surface epithelium neutrophils per x400 field absent of menstrual endometrium and/or > or =2 stromal plasma cells per x120 field. We detected M genitalium in 7 (14%) of the women tested: 6 (12%) in cervical specimens and 4 (8%) in endometrial specimens. We conclude that M genitalium is prevalent in the endometrium of women with nongonococcal, nonchlamydial PID.

Objective: We investigated changes in serum uric acid across pregnancy in women with gestational hyperuricemia at delivery, with and without preeclampsia, compared with normal pregnant and women with preeclampsia without gestational hyperuricemia., Study Design: This was a nested case-control study of 116 controls, 27 women with preeclampsia with predelivery hyperuricemia, 37 women with preeclampsia without predelivery hyperuricemia, and 35 women with gestational hypertension with hyperuricemia at delivery but without proteinuria. Serum uric acid and creatinine was measured across pregnancy., Results: Women with predelivery hyperuricemia, with and without preeclampsia, had increased uric acid concentrations across pregnancy compared with controls, after 25 weeks' gestation compared with women with preeclampsia without predelivery hyperuricemia. Adjusting for differences in glomerular filtration by serum creatinine accounted for part but not all of the increase in serum uric acid among women with preeclampsia and predelivery hyperuricemia., Conclusions: Among women with hyperuricemia at delivery, elevations in uric acid occur early. Multiple mechanisms may contribute to increased uric acid including changes in renal function.

The objective of this study was to quantify the mediating role of inflammation and triglycerides in the association between prepregnancy body mass index (weight (kg)/height (m)2) and preeclampsia. The authors conducted a nested case-control study of 55 preeclamptic women and 165 pregnant controls from the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001). Serum samples collected at < or = 20 weeks' gestation were analyzed for levels of C-reactive protein and triglycerides. The adjusted odds ratio (AOR) from a multivariable conditional logistic regression model assessing the total effect of body mass index on preeclampsia risk was compared with the AOR from the same model after results were controlled for C-reactive protein, triglycerides, and confounding factors (direct-effects model). The percentage of the total effect that was mediated through inflammation and triglycerides was calculated as 100 - [ln(direct-effects AOR)/ln(total-effects AOR)]. In the total-effects model, 4- and 8-unit increases in body mass index were associated with 1.7-fold (95% confidence interval (CI): 1.3, 2.3) and 2.9-fold (95% CI: 1.6, 5.2) increases in preeclampsia risk, whereas in the direct-effects model, these AORs were 1.4 (95% CI: 1.0, 1.9) and 2.0 (95% CI: 1.0, 3.8), respectively. Inflammation was a more important mediator than triglycerides. These findings suggest that approximately one third of the total effect of body mass index on preeclampsia risk is mediated through inflammation and triglyceride levels.

Endometrial cancer is the most common gynecologic malignancy in the United States. Substantial epidemiologic data implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a role in endometrial cancer development. Emerging laboratory data suggest that elevated levels of prostaglandin E(2) may underlie the transformation of normal endometrium to neoplastic tissue and that in vitro nonsteroidal anti-inflammatory drugs may inhibit endometrial cancer cell growth. In this review, we suggest that the risk factors for endometrial cancer--unopposed estrogens, anovulation, polycystic ovary syndrome, excessive menstruation, early menarche, and late menopause--may be viewed as factors increasing the exposure of the endometrium to inflammation, whereas pregnancy and smoking, two likely protective factors, have the opposite effect. Chronic inflammation can induce rapid cell division, increasing the possibility for replication error, ineffective DNA repair, and subsequent mutations. A proinflammatory milieu can also directly increase estrogen production. Hence, inflammation may work in conjunction with or in addition to estrogen exposure in the development of endometrial cancer.

Gestational hypertension is differentiated into higher and lower risk by the presence or absence of proteinuria. We asked if hyperuricemia, a common finding in pregnancy hypertension, might also be an indicator of increased risk. We examined fetal outcome data from 972 pregnancies collected from 1997 to 2002 in a nested case-control study. Participants were nulliparous with no known medical complications. The frequency of preterm birth, the duration of pregnancy, frequency of small-for-gestational-age infants, and birth weight centile were determined for pregnancies assigned to 8 categories by the presence or absence of combinations of hypertension, hyperuricemia, and proteinuria. In women with gestational hypertension, hyperuricemia was associated with shorter gestations and smaller birth weight centiles and increased risk of preterm birth and small-for-gestational-age infants. Hyperuricemia increased the risk of these outcomes in the presence or absence of proteinuria. Risk was also increased in a small group of women with hyperuricemia and proteinuria without hypertension. Women with only hypertension and hyperuricemia have similar or greater risk as women with only hypertension and proteinuria. Those with hypertension, proteinuria, and hyperuricemia have greater risk than those with hypertension and proteinuria alone. The risk of these outcomes increased with increasing uric acid. Hyperuricemia is at least as effective as proteinuria at identifying gestational hypertensive pregnancies at increased risk. Uric acid should be reexamined for clinical and research utility.

Introduction: Trauma has been suggested, in case series, as one of the nonatherosclerotic mechanisms leading to acute myocardial infarction (AMI), the leading cause of death in the US. AMI following non-penetrating injury has been shown to carry significant morbidity and mortality., Objective: To determine whether hospitalized injuries in a large multi state population are associated with increased risk of AMI during the initial hospital stay., Methods: Statewide injury hospital discharge data were collected from 19 states in 1997. Affected body regions of interest included thoracic, abdominal or pelvic, spine or back and blunt cardiac injury (BCI). The outcome of interest was AMI which was identified based on ICD-9-CM discharge diagnoses for the same visit. Unadjusted and adjusted multivariate logistic regression analyses were performed., Results: Independent of confounding factors and coronary arteriography (CA) status, BCI was associated with 2.6-fold increased risk for AMI in persons 46 years or older. When the diagnosis of AMI was confirmed by CA, BCI was associated with 8-fold risk elevation among patients 46 years and older and a 31-fold elevation among patients 45 years and younger. Abdominal or pelvic trauma, irrespective of confounding factors and CA status, was associated with a 65% increase in the risk of AMI among patients 45 years and younger and 93% increase in the risk of among patients 46 years and older. When the diagnosis of AMI was confirmed by CA, abdominal or pelvic trauma was associated with 6-fold risk elevation among patients 46 years and older., Conclusion: Direct trauma to the heart, as characterized by a diagnosis of BCI, was observed to carry the greatest risk for AMI. Abdominal or pelvic trauma also increased the risk for AMI. Longitudinal studies are warranted to better understand the relationship between trauma and AMI.

Purpose: A predisposition to coronary artery disease (CAD) may put women at risk for preeclampsia. Morbid preeclampsia (early, severe, recurrent, and with neonatal morbidity) represents the subset of preeclampsia of greatest public health concern., Methods: We review here the published links between preeclampsia and CAD., Results: Many risk factors are common to both CAD and preeclampsia. These include obesity; elevated blood pressure; dyslipidemia; insulin resistance; and hyperglycemia, together termed "Syndrome X"; as well as endothelial dysfunction; hyperuricemia; hyperhomocysteinemia; and abnormalities of inflammation, thrombosis, and angiogenesis. After pregnancy, women with preeclampsia are more likely to experience later life CAD., Conclusions: Both the association between CAD risk factors and preeclampsia and the association between preeclampsia and later CAD appears to be more pronounced among the subset of women with morbid preeclampsia. Thus, women at elevated risk for CAD may be at particularly high risk for morbid preeclampsia and women with morbid preeclampsia may be those at highest risk for later life CAD.

Objectives: Smoking, pregnancy, and preeclampsia are all associated with changes in markers of the metabolic syndrome. Several markers are increased in all three conditions. However, smoking is negatively associated with preeclampsia, and therefore some markers would be expected to behave differently in smokers during pregnancy. We compared several metabolic markers of the metabolic syndrome in healthy primigravid smokers and nonsmokers over normal pregnancy to explore mechanisms for the reduced risk of preeclampsia in smokers., Study Design: Plasma was obtained from 63 women throughout pregnancy who delivered at term. Smoking status was determined by urinary cotinine concentrations measured by HPLC. Uric acid, creatinine, free fatty acids, triglycerides, and total cholesterol were measured with diagnostic kits. Data were analyzed by repeated-measures ANOVA., Results: The smoking groups were not different by delivery gestational age, maternal age, body mass index, or race. Uric acid, cholesterol, and triglyceride concentrations increased during pregnancy (significant for time, P < 0.0001). Mean uric acid and creatinine concentrations were different by smoking status (P < 0.001 and P = 0.046). Nonsmokers had the lowest concentrations of uric acid, and women who quit smoking had the highest concentrations. Uric acid concentrations remained significantly different controlling for serum creatinine, Conclusions: Women have changes in markers of the metabolic syndrome during pregnancy, and uric acid is further influenced by smoking. The difference in uric acid concentrations by smoking status may be secondary to increased production through the xanthine oxidase pathway but is not simply a result of altered glomerular function because the association persists after controlling for creatinine.

Controversy surrounds the association between bacterial vaginosis (BV) and pelvic inflammatory disease (PID). Women (N = 1,140) were ascertained at five US centers, enrolled (1999-2001), and followed up for a median of 3 years. Serial vaginal swabs were obtained for Gram's stain and cultures. PID was defined as 1) histologic endometritis or 2) pelvic pain and tenderness plus oral temperature >38.8 degrees C, leukorrhea or mucopus, erythrocyte sedimentation rate >15 mm/hour, white blood cell count >10,000, or gonococcal/chlamydial lower genital infection. Exploratory factor analysis identified two discrete clusters of genital microorganisms. The first correlated with BV by Gram's stain and consisted of the absence of hydrogen peroxide-producing lactobacillus, Gardnerella vaginalis, Mycoplasma hominis, anaerobic gram-negative rods, and, to a lesser degree, Ureaplasma urealyticum. The second, unrelated to BV by Gram's stain, consisted of Enterococcus species and Escherichia coli. Being in the highest tertile in terms of growth of BV-associated microorganisms increased PID risk (adjusted rate ratio = 2.03, 95% confidence interval: 1.16, 3.53). Carriage of non-BV-associated microorganisms did not increase PID risk. Women with heavy growth of BV-associated microorganisms and a new sexual partner appeared to be at particularly high risk (adjusted rate ratio = 8.77, 95% confidence interval: 1.11, 69.2). When identified by microbial culture, a combination of BV-related microorganisms significantly elevated the risk of acquiring PID.

Context: Cardiac injury has been well recognised as a complication of blunt chest trauma. Its clinical spectrum ranges from blunt cardiac injury (BCI) to complete rupture of cardiac tissues, with cardiac valvular injury often being overlooked., Objective: To determine whether hospitalised BCI is associated with increased risk of cardiac valve insufficiency in a large multi-state hospitalised population., Methods: Cases with BCI and cardiac valve insufficiency were identified based on discharge diagnoses in 1997 statewide hospital discharge data from 19 states. Four valvular outcomes were studied: (1) mitral valve insufficiency, incompetence, regurgitation (MVIIR); (2) aortic valve insufficiency, incompetence, regurgitation, stenosis (AVIIRS); (3) tricuspid valve insufficiency, incompetence, regurgitation, stenosis (TVIIRS); and (4) pulmonary valve insufficiency, incompetence, regurgitation, stenosis (PVIIRS)., Results: Among 1,051,081 injury discharges, 2709 (0.26%) people had BCI; 13,087 (1.25%) had MVIIR; 9811 (0.93%) had AVIIRS; 1338 (0.13%) had TVIIRS; 178 (0.02%) had PVIIRS. Independent of potential confounding factors, discharge for BCI was associated with a 12-fold increased risk for TVIIRS and a 3.4-fold increased risk for AVIIRS., Conclusion: Cardiac valve insufficiency has been well recognised as an important risk factor for congestive heart failure. With the findings that BCI is associated with an increased risk of specific valvular disorders, it is possible that trauma may play an important and heretofore largely unrecognised role in a portion of the burden of cardiovascular morbidity and mortality.

Objective: Among all women with pelvic inflammatory disease (PID), prevention of adverse reproductive consequences appears to be similarly achieved by outpatient treatment and inpatient treatment. We assessed whether outpatient is as effective as inpatient treatment in relevant age, race, and clinical subgroups of women with PID., Methods: Women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease (n = 831) were randomized into a multicenter trial of inpatient treatment, initially employing intravenous cefoxitin and doxycycline compared with outpatient treatment consisting of a single intramuscular injection of cefoxitin and oral doxycycline. Comparisons between treatment groups during a mean of 84 months of follow-up were made for pregnancies, live births, time to pregnancy, infertility, PID recurrence, chronic pelvic pain, and ectopic pregnancy., Results: Outpatient treatment assignment did not adversely impact the proportion of women having one or more pregnancies, live births, or ectopic pregnancies during follow-up; time to pregnancy; infertility; PID recurrence; or chronic pelvic pain among women of various races; with or without previous PID; with or without baseline Neisseria gonorrhoeae and/or Chlamydia trachomatis infection; and with or without high temperature/white blood cell count/pelvic tenderness score. This was true even in teenagers and women without a previous live birth. Ectopic pregnancies were more common in the outpatient than the inpatient treatment group, but because these were so rare, the difference did not reach statistical significance (5 versus 1, odds ratio 4.91, 95% confidence interval 0.57-42.25)., Conclusion: Among all women and subgroups of women with mild-to-moderate PID, there were no differences in reproductive outcomes after randomization to inpatient or outpatient treatment., Level of Evidence: I.

Reproductive failure in a variety of forms, whether it be infertility, miscarriage, pre-eclampsia, prematurity or intrauterine growth restriction, may aggregate within individuals. This observation, although rarely studied, suggests that single pathophysiologies may be associated with a variety of reproductive morbidities. In this review, hyperimmune responsiveness to pregnancy is provided as one example of a process leading to a multitude of adverse impacts on healthy childbearing. Further research on reproductive failure as a spectrum is warranted.

Purpose: To explore the dose-dependent relation between prepregnancy body mass index (BMI) and the risk of preeclampsia after adjusting for measured confounders., Methods: We studied 1179 primiparous women who enrolled at < 16 weeks' gestation into a prospective cohort study of the pathogenesis of preeclampsia. Multivariable logistic regression was used to quantify the independent effect of prepregnancy BMI on the risk of preeclampsia after adjusting for race and smoking status. BMI was specified as a restricted quadratic spline., Results: Preeclampsia risk rose strikingly from a BMI of 15 to 30 kg/m(2). Compared with women with a BMI of 21, the adjusted risk of preeclampsia doubled at a BMI of 26 (odds ratio 2.1 [95% confidence interval, 1.4, 3.4]), and nearly tripled at a BMI of 30 (2.9 [1.6, 5.3]). Women with a BMI of 17 had a 57% reduction in preeclampsia risk compared with women with a BMI of 21 (0.43 [0.25, 0.76]), and a BMI of 19 was associated with a 33% reduction in risk (0.66 [0.50, 0.87])., Conclusions: These results indicate that preeclampsia risk rises through most of the BMI distribution. The dramatic elevation in overweight prevalence in the United States may increase preeclampsia incidence in the future.

Context: An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease., Objective: We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates., Study Design: This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta)., Results: sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ., Conclusions: These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

Oral contraceptive (OC) use has been consistently linked to a reduction in ovarian cancer in a dose-dependent fashion. Whether short-term OC use is protective remains controversial. In 1994-1998 in the Delaware Valley of Pennsylvania, the authors examined the association between short-term OC use and ovarian cancer in a population-based case-control study comparing 608 incident epithelial ovarian cancer cases with 926 community controls. Using unconditional logistic regression and adjusting for known confounders, they found a significant reduction in ovarian cancer risk for women who had used OCs for < or =6 months (odds ratio = 0.73, 95% confidence interval: 0.54, 0.99). This protective effect was observed in only that group who had used OCs for < or =6 months and stopped because of side effects (odds ratio = 0.59, 95% confidence interval: 0.40, 0.87 for side effects and odds ratio = 0.91, 95% confidence interval: 0.60, 1.37 for non-side-effects). Women who used OCs for >6 months were at a reduced risk independent of their reason for stopping. Results were similar when stratifying by parity and hormone therapy use. Thus, OC use for as little as 6 months provides significant protection against ovarian cancer risk, protection that appears limited to those women who stop using OCs because of side effects. Mediating factors may reflect endogenous hormone levels, OC metabolism, or OC bioactivity.

Objective: The objective of this study was to compare the demographic, clinical, and microbiologic findings in women with subclinical pelvic inflammatory disease (PID) and women with acute PID., Study: A cross-sectional study was performed using cohorts from 2 separate studies of 1293 women at risk for PID. Most participants were recruited from emergency departments, sexually transmitted disease clinics, and family planning clinics in metropolitan centers. We compared demographic, clinical, and microbiologic findings among women with acute PID, women with subclinical PID, and women without endometritis (controls). Statistical analyses included chi-square for categorical variables, calculation of odds ratio and 95% confidence intervals, and polychotomous logistic regression when appropriate., Results: Similar proportions of women with acute and subclinical PID tested positive for cervical Chlamydia trachomatis (odds ratio [OR], 1.1; 95% confidence interval, 0.6-2.0) and had bacterial vaginosis (OR, 0.7; 95% CI, 0.2-1.8). The rate of cervical Neisseria gonorrhoeae infection in women with subclinical PID was intermediate between the rates in women with acute PID and controls (21% vs. 49% vs. 7%, respectively, P <0.001, test for trend). Endometrial recovery of N. gonorrhoeae and C. trachomatis in women with subclinical PID was also seen at intermediate levels. Similar distributions of teenagers, women who smoked or used illicit drugs, and women engaging in sexual intercourse during menses were found in each group. Proportions of women with subclinical PID who were black and with lower education levels were intermediate between the proportions of these characteristics in women with acute PID and controls., Conclusion: Demographic and microbiologic characteristics of women with subclinical and acute PID are comparable. These findings suggest that the pathophysiological mechanisms of acute and subclinical PID are similar.

Objective: The objective of this study was to assess in prospective data whether bacterial vaginosis (BV) is associated with gonococcal/chlamydial cervicitis., Study: A total of 1179 women at high risk for sexually transmitted infections was followed for a median of 3 years. Every 6 to 12 months, vaginal swabs were obtained for Gram stain, culture of microflora, and Neisseria gonorrhoeae and Chlamydia trachomatis. A Gram stain score of 7 to 10 based on the Nugent criteria categorized BV., Results: Baseline BV was associated with concurrent gonococcal/chlamydial infection (adjusted odds ratio, 2.83; 95% confidence interval [CI], 1.81-4.42). However, the association between BV and subsequent, incident gonococcal/chlamydial genital infection was not significant (adjusted relative risk [RR], 1.52; 95% CI, 0.74-3.13). Dense growth of pigmented, anaerobic Gram-negative rods (adjusted RR, 1.93; 95% CI, 0.97-3.83) appeared to elevate the risk for newly acquired gonococcal/chlamydial genital infection., Conclusions: BV was common among a predominantly black group of women with concurrent gonococcal/chlamydial infection but did not elevate the risk for incident infection.

Objective: We measured maternal serum soluble fms-like tyrosine kinase 1 concentrations across pregnancy and immediately postpartum in women who developed preeclampsia and normal pregnant women., Study Design: This was a nested case control study of 113 normal pregnant women and 55 women with preeclampsia., Results: Serum soluble fms-like tyrosine kinase 1 concentrations increased similarly in early pregnancy in both groups. Mean serum soluble fms-like tyrosine kinase 1 concentrations were increased in women who developed preeclampsia, compared with normal pregnant women, and this increase was most pronounced in severe preeclampsia. However, many women with preeclampsia had soluble fms-like tyrosine kinase 1 concentrations similar to normal pregnant women. Lastly, soluble fms-like tyrosine kinase 1 decreased rapidly after delivery, but this decrease was significantly slower in women with severe preeclampsia., Conclusion: Increased soluble fms-like tyrosine kinase 1 is not an early-pregnancy event among women who later develop preeclampsia. Increased soluble fms-like tyrosine kinase 1 is more likely to be present in women with severe preeclampsia, but it is not present in all women with preeclampsia. Soluble fms-like tyrosine kinase 1 concentrations decrease more slowly after delivery in women with preeclampsia, consistent with a decreased rate of excretion or continued production.

In a previous analysis, we reported an inverse association of dietary calcium intake with the risk of ovarian cancer (Goodman et al. 2002. Am J Epidemiol 156:148-57). The CALCA gene codes for calcitonin, an important regulator of bone calcium metabolism. Data from a population-based case-control study conducted in Hawaii were used to examine the hypothesis that a T --> C transition 624 base pairs upstream (-624) of the translation initiation codon of the CALCA gene influences the risk of ovarian malignancy. A structured interview was conducted for 182 histologically confirmed ovarian cancer cases and 219 controls. Blood specimens were collected from the subjects at their homes. A significant negative trend (P for trend: 0.02) in the odds ratios (ORs) was found with increasing intake of calcium. Women with any CALCA C allele were at nonsignificantly higher risk of ovarian cancer (OR: 1.5, 95% CI: 0.9-2.3) compared to women with the TT genotype and the risk increased with the number of C alleles (P for trend: 0.05). When further analyzed within ethnic subgroups, a significant positive association was found among Japanese for CALCA CT (OR: 2.3, 95% CI: 1.0-5.3) and CALCA CC (OR: 7.2, 95% CI: 1.1-46.0) compared with Japanese women who were homozygous for the T allele. The trend in risk associated with the C allele was most significant among women who had used oral contraceptives (P for trend: 0.05), had been pregnant (P for trend: 0.04), and had nonmucinous histological types of ovarian cancer (P for trend: 0.02). However, the association of ovarian cancer risk with the CALCA genotype was not significantly modified by any of the dietary, nondietary, or clinical variables included in this study. These preliminary data suggest a strong positive association of the CALCA C allele with the risk of ovarian cancer among some subgroups., ((c) 2005 Wiley-Liss, Inc.)

Objective: The purpose of this study was to examine the relationship between cytokine genotypes and preeclampsia., Study Design: We conducted a case-control study that examined cytokine genotypes among 150 primiparous preeclamptic women and 661 primiparous, normotensive women. Analyses were adjusted for age, prepregnancy cigarette smoking, and education., Results: Preeclamptic white women were more likely than normotensive white women to carry the up-regulating tumor necrosis factor-alpha-308 A/A (odds ratio, 4.1; 95% CI, 1.1-15.3) genotype. Both black and white women with preeclampsia were more likely than normotensive control subjects to carry the interleukin-1alpha-producing-4845 G/G genotype (black odds ratio, 11.6; 95% CI, 1.5-89.3; white odds ratio, 1.7; 95% CI, 0.7-3.9), -889 C/C genotype (black odds ratio, 5.1; 95% CI, 0.6-41.6; white odds ratio, 1.9; 95% CI, 0.8-4.7), and the interleukin-1alpha-4845/interleukin-1alpha-889/interleukin-1beta-3957 GCC/GCC haplotype (black odds ratio, 3.4; 95% CI, 1.3-8.7; white odds ratio, 2.1; 95% CI, 1.4-3.2)., Conclusion: Cytokine genotypes were associated with preeclampsia and may identify women who are at high risk for preeclampsia.

Background: Testing of urine samples is noninvasive and could overcome several barriers to screening for chlamydial and gonococcal infections, but most test samples are obtained directly from the cervix or urethra., Purpose: To systematically review studies that assessed the sensitivity and specificity of nucleic acid amplification tests for Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens and to compare test characteristics according to type of assay, site of sample collection, presence of symptoms, disease prevalence, and characteristics of the reference standard., Data Sources: Relevant studies in all languages were identified by searching the MEDLINE database (January 1991 to December 2004) and by hand-searching the references of identified articles and relevant journals., Study Selection: Studies were selected that evaluated 1 of 3 commercially available nucleic acid amplification tests, included data from tests of both a urine sample and a traditional sample (obtained from the cervix or urethra), and used an appropriate reference standard., Data Extraction: From 29 eligible studies, 2 investigators independently abstracted data on sample characteristics, reference standard, sensitivity, and specificity., Data Synthesis: Articles were assessed qualitatively and quantitatively. Summary estimates for men and women were calculated separately for chlamydial and gonococcal infections and were stratified by assay and presence of symptoms. The pooled study specificities of each of the 3 assays exceeded 97% when urine samples were tested, for both chlamydial infection and gonorrhea and in both men and women. The pooled study sensitivities for the polymerase chain reaction, transcription-mediated amplification, and strand displacement amplification assays, respectively, were 83.3%, 92.5%, and 79.9% for chlamydial infections in women; 84.0%, 87.7%, and 93.1% for chlamydial infections in men; and 55.6%, 91.3%, and 84.9% for gonococcal infections in women. The pooled specificity of polymerase chain reaction to gonococcal infections in men was 90.4%. In subgroup analyses, the sensitivity did not vary according to the prevalence of infection or the presence of symptoms but did vary according to the reference standard used., Limitations: Few published studies present data on the transcription-mediated amplification or strand displacement amplification assays, and few studies report data from asymptomatic patients or low-prevalence groups., Conclusions: Results of nucleic acid amplification tests for C. trachomatis on urine samples are nearly identical to those obtained on samples collected directly from the cervix or urethra. Although all 3 assays can also be used to test for N. gonorrhoeae, the sensitivity of the polymerase chain reaction assay in women is too low to recommend its routine use to test for gonorrhea in urine specimens.

Objective: The objective of the present study was to evaluate the cardiovascular risk profile and the prevalence of metabolic syndrome among women with a history of pregnancy-induced hypertension (PIH)., Methods: From a cohort of 3,799 nulliparous women prospectively recruited between 1989 and 1997, we performed an observational study on 168 case-control pairs 7.8 years after delivery. Participants were scheduled for a visit with a research nurse to evaluate their cardiovascular risk profile using a questionnaire, anthropometric measurements and blood specimen analysis., Results: One hundred sixty-eight women with prior PIH (105 with gestational hypertension and 63 with preeclampsia) and 168 controls matched for age and year of index delivery were evaluated. The women with PIH (34.6 +/- 4.4 years) were more obese and had higher systolic (115 mm Hg versus 108 mm Hg) and diastolic (75 mm Hg versus 70 mm Hg) blood pressures (P < .001) than the 168 controls (35.1 +/- 4.5 years). They had lower high-density lipoprotein cholesterol level (1.30 mmol/L versus 1.42 mmol/L; P < .001), increased fasting blood glucose concentration (5.2 mmol/L versus 5.0 mmol/L; P = .002), and higher insulin levels (119 versus 91 pmol/L; P < .001). The prevalence of the metabolic syndrome was higher in the PIH group (unadjusted odds ratio = 4.9; 95% confidence interval 2.1-10.9) compared with controls, even after adjustment for confounders (adjusted odds ratio = 3.6; 95% confidence interval 1.4 -9.0)., Conclusion: In white women in their mid-30s, the prevalence of the metabolic syndrome is 3- to 5-fold increased in those with a history of PIH in their first pregnancy. This emphasizes the importance of long-term follow-up assessment for cardiovascular risk factors in these women.

Prenatal exposure to tobacco smoke has been associated with an increased risk of pediatric malignancies, yet the transplacental induction of genetic alterations by tobacco smoke carcinogens and their implication to childhood diseases remain poorly understood. We characterized mutations in the HPRT gene in umbilical cord blood T-lymphocytes of self-reported 103 never-smoking mothers and 104 smoking mothers (54 mothers smoked throughout and 50 mothers quit smoking during pregnancy). The results showed the illegitimate V(D)J recombinase-mediated deletion of HPRT exons 2-3 was the most prominent alteration occurring in 48.2% (26/54) of mutants from neonates of the smoking mothers who smoked during pregnancy, compared with 28.0% (14/50) from those of smoking mothers who quit smoking during pregnancy (p=0.035, Fisher's exact test), 34.9% (36/103) from never-smoking mothers (p=0.08), or 32.7% (50/153) of those of neonates born from the latter two groups of mothers combined (p=0.043). There was no significant difference in the frequency of this deletion between neonates of the never-smoking mothers and the smoking mothers who quit smoking during pregnancy (34.9% versus 28.0%, respectively, p=0.39). The results show an increase in illegitimate V(D)J recombinase-mediated deletion of HPRT exons 2-3 in cord blood T-lymphocytes of newborns of mothers who smoked during pregnancy, compared with the group of mothers who did not smoke during pregnancy, implying an increase in illegitimate V(D)J recombinase-mediated alteration, a genetic recombination event associated with childhood malignancies, may be induced in utero during pregnancy by maternal exposure to tobacco smoke-derived genotoxicants.

Objective: The objective of this study was to assess the risk profile for chronic pelvic pain (CPP) after pelvic inflammatory disease (PID)., Study: Multivariate logistic regression was used to assess risk factors for CPP in a longitudinal study of 780 predominately black, urban women with clinically suspected PID: complaints of acute pain (<30 days); a clinical finding of pelvic tenderness; and leukorrhea, mucopurulent cervicitis, or untreated gonococcal or chlamydial cervicitis. CPP was defined as pain reported at >or=2 consecutive interviews conducted every 3 to 4 months for 2 to 5 years., Results: Nonblack race (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.31-3.58), being married (OR, 2.06; 95% CI, 1.02-4.18), a low SF-36 mental health composite score (OR, 2.71; 95% CI, 1.69-4.34), >or=2 prior PID episodes (OR, 2.84; 95% CI, 1.07-7.54), and smoking (OR, 1.65; 95% CI, 1.01-2.71) independently predicted CPP. Histologic endometritis or evidence of endometrial Neisseria gonorrhoeae or Chlamydia trachomatis infection was negatively associated with CPP (OR, 0.69; 95% CI, 0.44-1.10)., Conclusions: A range of demographic, clinical, historical, and behavioral factors predict CPP after PID.

Objective: Oral contraceptives (OCs) have been consistently linked to reduced risk of ovarian cancer. Oral contraceptive formulations display varying degrees of androgenicity. Data linking androgens to ovarian cancer suggest that OC androgenicity may impact efficacy in preventing ovarian cancer. The authors investigated whether OC efficacy might differ according to androgenicity by using data from a large, population-based, case-control study (the Steroid Hormones and Reproductions [SHARE] Study)., Methods: Detailed data on OC formulation was obtained by an in-person interview for 568 cases and 1,026 controls. Multivariable logistic regression was used to assess the association of OC androgenicity with ovarian cancer while controlling for the known potential confounders of age, parity, family history of ovarian cancer, and tubal ligation., Results: Androgenic and nonandrogenic OCs conferred a similar and significant reduction in ovarian cancer risk (odds ratio 0.52, 95% confidence interval 0.35-0.76 and odds ratio 0.59, 95% confidence interval 0.45-0.78, respectively). No differences in duration of use, age at first use, and time since last use were found between androgenic and nonandrogenic formulations., Conclusion: In general, the androgenicity of an OC does not alter chemopreventive efficacy., Level of Evidence: II-2.

While the protective nature of parity with respect to ovarian cancer has been well documented, whether a history of incomplete pregnancy affects ovarian cancer risk is uncertain. Data collected from 739 epithelial ovarian cancer cases and 1,313 community controls in the Delaware Valley from 1994 to 1998 were used to evaluate the relation between gestational length and timing of first induced or spontaneous abortion and ovarian cancer risk. Incomplete pregnancy was not associated with ovarian cancer among nulliparous women or among ever-pregnant women either before or after adjustment for relevant confounders (for nulliparous women, odds ratio (OR) = 1.12, 95% confidence interval (CI): 0.66, 1.89; for ever-pregnant women, OR = 0.95, 95% CI: 0.76, 1.18). Among unigravid women, one full-term pregnancy was more protective than an incomplete pregnancy (adjusted OR = 0.29, 95% CI: 0.15, 0.57). These results were independent of the type of pregnancy loss. Among ever-pregnant women, a spontaneous abortion before a first birth provided significant protection (adjusted OR = 0.47, 95% CI: 0.30, 0.75), while no significant effect was found for an induced abortion prior to a first birth (adjusted OR = 0.80, 95% CI: 0.44, 1.47). These data do not support an independent association between incomplete pregnancies, either spontaneous or induced, and ovarian cancer risk.

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.

Objective: Recent studies of ovarian cancer have suggested a role for inflammation in carcinogenesis. Data from a population-based case-control study in Hawaii were examined to assess the relation between polymorphisms in cytokines involved with the inflammatory response, specifically members of the interleukin (IL) family and the incidence of ovarian cancer., Patients and Methods: The analysis of 182 epithelial ovarian cancer cases and 219 controls focused on the polymorphisms in the following genes: IL-1alpha, IL-1beta, IL-6, IL-10, and IL-18. Genotype data were obtained from blood samples collected in participants' homes, and reproductive, demographic, and lifestyle histories were collected during interview., Results: There were no significant odds ratios (ORs) for ovarian cancer by allelic variants in any of the IL genes after adjusting for age, ethnicity, education, oral contraceptive pill use, pregnancy, and history of tubal ligation. Although there was a significantly reduced risk of ovarian cancer risk among women with an IL-1alpha (-4845) T allele compared to women with two G alleles (OR: 0.59; 95% confidence interval: 0.37-0.97) after adjustment for age and ethnicity, the trend was not significant (p = 0.10). Further examination of the data suggested that women with at least one IL-18 variant allele (a G to C transition at position -137) were at significantly decreased risk of advanced ovarian cancer (OR: 0.51; 95% confidence interval: 0.28-0.90) compared to women with the IL-18 GG genotype. There was a significant difference in the risk of ovarian cancer associated with the IL-18 C allele by stage at diagnosis (p = 0.04 for homogeneity in the ORs): cases with IL-18 GC or CC genotypes were less likely to be diagnosed at regional/distant stages. Analysis of the data within ethnic subgroups revealed a significant positive association of the heterozygous IL-18 GC genotype with ovarian cancer risk among Native Hawaiian women (OR: 9.96; 95% CI: 1.88-52.90). The OR for ovarian cancer was not significant for Native Hawaiian women homozygous for the IL-18 C allele, but only one case and control had the IL-18 CC genotype., Conclusions: Overall, this study does not support an association of selected IL-1alpha, IL-1beta, IL-6, IL-10, or IL-18 polymorphisms with the risk for ovarian cancer. However, the IL-18 G137C variant may be a marker for ovarian cancer progression or metastasis.

Innate and adaptive immune responsiveness is variable within the population. Since robust immune reactions are critical to the survival of humans, the existence of immune variability in the population suggests the existence of competing, alternative phenotypes. Although women with powerful immune responsiveness may be more likely to survive to reproduce, their reproductive experiences may be less successful than women who are not as responsive. Normal pregnancy elicits a maternal inflammatory reaction. This can be understood on the basis of maternal-fetal conflict theory: inflammation is a component of the maternal attempt to limit excessive fetal demands. However, an overly aggressive inflammatory reaction has been shown to relate to a variety of adverse reproductive outcomes. Reviewed here are several examples, including the fallopian tube damage that results from pelvic inflammatory disease, the upregulated inflammatory response among women who develop preeclampsia, an association between immune hyperresponsiveness and premature delivery, and the relationship between autoimmune diseases and multiple adverse pregnancy outcomes. The hypothesis that immune hyperresponsiveness limits reproductive capacity suggests many avenues for research.

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

Racial disparities in health are largely unexplained. Because many diseases causing premature mortality among African Americans are mediated by the immune system, the authors explored the race-specific distribution of allelic variants in cytokine genes known to stimulate inflammation. The authors studied women seeking prenatal care and delivering singletons in uncomplicated first births at a US hospital in 1997-2001. A total of 179 African-American women and 396 White women were evaluated for functionally relevant allelic variants in cytokine genes. African-American women were significantly more likely to carry allelic variants known to up-regulate proinflammatory cytokines; odds ratios increased with allele dose. Odds ratios for African Americans versus Whites in genotypes up-regulating proinflammatory interleukin (IL) 1 (IL1A-4845G/G, IL1A-889T/T, IL1B-3957C/C, and IL1B-511A/A) ranged from 2.1 to 4.9. The proinflammatory cytokine interleukin-6 IL6-174 G/G genotype was 36.5 times (95% confidence interval (CI): 8.8, 151.9) more common among African Americans. Genotypes known to down-regulate the antiinflammatory interleukin-10 (IL10-819 T/T and IL10-1082 A/A) were elevated 3.5-fold (95% CI: 1.8, 6.6) and 2.8-fold (95% CI: 1.6, 4.9) in African Americans. Cytokine genotypes found to be more common in African-American women were consistently those that up-regulate inflammation.

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