Maternal and neonatal outcomes associated with treating hypertension in pregnancy at different thresholds.

INTRODUCTION: In the United States, there has been controversy over whether treatment of mild-to-moderate hypertension during pregnancy conveys more benefit than risk. OBJECTIVE: The objective of the study was to compare risks and benefits of treatment of mild-to-moderate hypertension during pregnancy. METHODS: This retrospective cohort study included 11,871 pregnant women with mild-to-moderate hypertension as defined by blood pressure (BP) values from three Kaiser Permanente regions between 2005 and 2014. Data were extracted from electronic health records. Dynamic marginal structural models with inverse probability weighting and informative censoring were used to compare risks of adverse outcomes when beginning antihypertensive medication treatment at four BP thresholds (≥155/105, ≥150/100, ≥145/95, ≥140/90 mm Hg) compared with the recommended threshold in the United States at that time, ≥160/110 mm Hg. Outcomes included preeclampsia, preterm birth, small-for-gestational-age (SGA), Neonatal Intensive Care Unit (NICU) care, and stillbirth. Primary analyses allowed 2 weeks for medication initiation after an elevated BP. Several sensitivity and subgroup (i.e., race/ethnicity and pre-pregnancy body mass index) analyses were also conducted. RESULTS: In primary analyses, medication initiation at lower BP thresholds was associated with greater risk of most outcomes. Comparing the lowest (≥140/90 mm Hg) to the highest BP threshold (≥160/110 mm Hg), we found an excess risk of preeclampsia (adjusted Risk Difference (aRD) 38.6 per 100 births, 95% Confidence Interval (CI): 30.6, 46.6), SGA (aRD: 10.2 per 100 births, 95% CI: 2.6, 17.8), NICU admission (aRD: 20.2 per 100 births, 95% CI: 12.6, 27.9), and stillbirth (1.18 per 100 births, 95% CI: 0.27, 2.09). The findings did not reach statistical significance for preterm birth (aRD: 2.5 per 100 births, 95% CI: -0.4, 5.3). These relationships were attenuated and did not always reach statistically significance when comparing higher BP treatment thresholds to the highest threshold (i.e., ≥160/110 mm Hg). Sensitivity and subgroup analyses produced similar results. CONCLUSIONS: Initiation of antihypertensive medication at mild-to-moderate BP thresholds (140-155/90-105 mm Hg; with the largest risk consistently associated with treatment at 140/90 mm Hg) may be associated with adverse maternal and neonatal outcomes. Limitations include inability to measure medication adherence.

Breastfeeding history and adenomyosis risk using a novel case-control study design.

OBJECTIVE: To evaluate the association between breastfeeding history, including lifetime exclusive breastfeeding, and risk of adenomyosis. DESIGN: We used data from a case-control study designed with 2 control groups to address the challenge of selecting noncases for a valid epidemiologic study when cases are identified by hysterectomy. The case-control study was conducted among premenopausal and postmenopausal enrollees aged 18-59 years in a large, integrated health care system in western Washington state. PATIENT(S): Cases were enrollees with incident, pathology-confirmed adenomyosis diagnosed during 2001-2006 (n = 386). The 2 control groups were as follows: (1) randomly selected age-matched enrollees with intact uteri ("population controls," n = 323) and (2) hysterectomy controls (n = 233). INTERVENTION(S): Data on breastfeeding history were collected by in-person interviews. For each reported live birth, participants were asked whether they breastfed, along with infant age at supplemental feeding introduction and breastfeeding discontinuation. MAIN OUTCOME MEASURE(S): Among participants with at least 1 live birth (330 cases, 246 population controls, and 198 hysterectomy controls), we used unconditional logistic regression to estimate adjusted odds ratios and 95% confidence intervals (CIs) for the associations between the following: (1) ever breastfeeding, (2) ever breastfeeding for ≥8 weeks, (3) lifetime breastfeeding, and (4) lifetime exclusive breastfeeding and risk of adenomyosis. Analyses were adjusted for age, reference year, smoking, education, and parity. RESULT(S): In analyses comparing cases with population controls, we observed a 40% decreased odds of adenomyosis with a history of ever breastfeeding (adjusted odds ratio, 0.6; 95% CI, 0.3-1.0) and breastfeeding for ≥8 weeks (adjusted odds ratio, 0.6; 95% CI, 0.4-0.8). The strongest associations, 60%-70% decreased odds of adenomyosis, were observed with ≥12 months of lifetime breastfeeding (vs. <3 months) (adjusted odds ratio, 0.4; 95% CI, 0.2-0.6) and 9 to <12 months of lifetime exclusive breastfeeding (vs. <3 months) (adjusted odds ratio, 0.3; 95% CI, 0.2-0.6), comparing cases to population controls. In analyses using hysterectomy controls, we observed similar patterns of associations slightly attenuated in magnitude. CONCLUSION(S): Breastfeeding history was associated with a 40% decreased odds of adenomyosis, a condition that can confer substantial morbidity and requires hysterectomy for definitive treatment. The consistency of our findings with that of a previous study lends support that breastfeeding may modify risk of adenomyosis.

Identifying hypertensive disorders of pregnancy, a comparison of two epidemiologic definitions.

Introduction: Studies of hypertension in pregnancy that use electronic health care data generally identify hypertension using hospital diagnosis codes alone. We sought to compare results from this approach to an approach that included diagnosis codes, antihypertensive medications and blood pressure (BP) values. Materials and methods: We conducted a retrospective cohort study of 1,45,739 pregnancies from 2009 to 2014 within an integrated healthcare system. Hypertensive pregnancies were identified using the "BP-Inclusive Definition" if at least one of three criteria were met: (1) two elevated outpatient BPs, (2) antihypertensive medication fill plus an outpatient hypertension diagnosis, or (3) hospital discharge diagnosis for preeclampsia or eclampsia. The "Traditional Definition" considered only delivery hospitalization discharge diagnoses. Outcome event analyses compared rates of preterm delivery and small for gestational age (SGA) between the two definitions. Results: The BP-Inclusive Definition identified 14,225 (9.8%) hypertensive pregnancies while the Traditional Definition identified 13,637 (9.4%); 10,809 women met both definitions. Preterm delivery occurred in 20.9% of BP-Inclusive Definition pregnancies, 21.8% of Traditional Definition pregnancies and 6.6% of non-hypertensive pregnancies; for SGA the numbers were 15.6, 16.3, and 8.6%, respectively (p < 0.001 for all events compared to non-hypertensive pregnancies). Analyses in women meeting only one hypertension definition (21-24% of positive cases) found much lower rates of both preterm delivery and SGA. Conclusion: Prevalence of hypertension in pregnancy was similar between the two study definitions. However, a substantial number of women met only one of the study definitions. Women who met only one of the hypertension definitions had much lower rates of adverse neonatal events than women meeting both definitions.

Maternal and neonatal outcomes of antihypertensive treatment in pregnancy: A retrospective cohort study.

OBJECTIVE: To compare maternal and infant outcomes with different antihypertensive medications in pregnancy. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente, a large healthcare system in the United States. POPULATION: Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension. METHODS: We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding. MAIN OUTCOME MEASURES: Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks. RESULTS: Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other ß-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication. CONCLUSIONS: Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.

Gestational weight gain and adverse pregnancy outcomes by pre-pregnancy BMI category in women with chronic hypertension: A cohort study.

OBJECTIVES: It is important to understand relationships of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension, given their high baseline risk of adverse outcomes. We assessed associations of gestational weight gain with adverse pregnancy outcomes in women with chronic hypertension by pre-pregnancy body mass index categories. STUDY DESIGN: We identified 14,369 women with chronic hypertension using electronic health records from 3 integrated health care delivery systems (2005-2014). Gestational weight gain-for-gestational age charts were used to calculate gestational weight gain z-scores, which account for gestational age. Modified Poisson regression models using generalized estimating equations were used to calculate relative risks and 95% confidence intervals, adjusted for sociodemographic and medical characteristics. MAIN OUTCOME MEASUREMENTS: Preeclampsia, preterm delivery, cesarean delivery, neonatal intensive care unit admission, birthweight (extracted from the electronic health record). RESULTS: In women with normal weight or overweight, low gestational weight gain (z-score < -1) was associated with 27-28% greater risk of preterm delivery and 48-82% greater risk of small-for-gestational age birthweight, while high gestational weight gain (z-score > 1) was associated with 40-90% greater risk of preeclampsia and 59-113% greater risk of large-for-gestational age birthweight. In women with obesity, low gestational weight gain was associated with 27-54% lower risk of several adverse pregnancy outcomes, including preeclampsia and cesarean delivery. CONCLUSIONS: In women with chronic hypertension and normal weight or overweight, moderate gestational weight gain may confer the lowest risk of adverse outcomes. In women with chronic hypertension and obesity, low gestational weight gain may be necessary for the lowest risk of adverse pregnancy outcomes.

Use of multiple failure models in injury epidemiology: a case study of arrest and intimate partner violence recidivism in Seattle, WA.

BACKGROUND: Single-failure survival models are commonly used in injury research. We aimed to demonstrate the application of multiple failure survival models in injury research by measuring the association between arrest and IPV recidivism. METHODS: We used data from a population-based cohort of 5466 male-female couples with a police-reported, male-perpetrated incident of IPV against their female partners that occurred in Seattle, WA during 1999-2001. We estimated the risk of physical and psychological IPV recidivism (separately) for the 12 months following the index event, according to perpetrator arrest or non-arrest for the index event. We used time-dependent extended Cox regression analyses for time-to-first IPV event and Prentice, Williams and Peterson model-based analyses for time-to-multiple IPV events. RESULTS: Arrest was associated with a reduction in time-to-first physical IPV recurrence but was not associated with time-to-first psychological IPV recurrence during the 12-month follow-up. Arrest was associated with a significantly decreased risk of physical and psychological IPV during the 12-month follow-up in the multiple failure models. The association between arrest and lower risk of physical IPV recidivism increased with increasing number of follow-up IPV events. CONCLUSIONS: We found arrest to be a plausible deterrent for recurrent IPV reduction. Our study also illustrates the use of multiple failure survival analyses in injury research. Such techniques facilitate inference about estimands that may have greater public health relevance and properly account for injury recurrence. By using multiple failure models, we were able to more deeply understand the relationship between arrest and IPV over time.

Early-life factors and endometriosis risk.

OBJECTIVE: To study early-life factors in relation to endometriosis risk in adulthood. DESIGN: Population-based case-control study. SETTING: Integrated healthcare system. PATIENT(S): Cases (n = 310) were women diagnosed for the first time with endometriosis between the years 1996 and 2001, and controls (n = 727) were women without a diagnosis of endometriosis randomly selected from the healthcare system population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the associations between intrauterine diethylstilbestrol (DES) exposure, maternal smoking, mother's age at delivery, firstborn status, birth weight, fetal number, prematurity, and regular soy formula feeding during infancy and endometriosis were estimated using unconditional logistic regression, adjusting for frequency matching and confounding variables. Information on early-life factors was ascertained retrospectively by in-person interview, with information on maternal DES use and regular soy formula feeding directly gathered from the participant's mother or other family member. RESULT(S): We observed that women who were regularly fed soy formula as infants had more than twice the risk of endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9-3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for frequency matching variables), although these confidence intervals included the null. CONCLUSION(S): Our results support the hypothesis that disruption of development during fetal and infant periods may increase the risk of endometriosis in adulthood.

A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis.

STUDY QUESTION: Is bisphenol A (BPA) exposure associated with the risk of endometriosis, an estrogen-driven disease of women of reproductive age? SUMMARY ANSWER: Our study suggests that increased urinary BPA is associated with an increased risk of non-ovarian pelvic endometriosis, but not ovarian endometriosis. WHAT IS KNOWN ALREADY: BPA, a high-volume chemical used in the polymer industry, has been the focus of public and scientific concern given its demonstrated estrogenic effects in vivo and in vitro and widespread human exposure. Prior studies of BPA and endometriosis have yielded inconsistent results and were limited by the participant sampling framework, small sample size or use of serum (which has very low/transient concentrations) instead of urine to measure BPA concentrations. STUDY DESIGN, SIZE, DURATION: We used data from the Women's Risk of Endometriosis study, a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the US Pacific Northwest. Cases were women with incident, surgically confirmed endometriosis diagnosed between 1996 and 2001 and controls were women randomly selected from the defined population that gave rise to the cases, without a current or prior diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Total urinary BPA concentrations were measured in 143 cases and 287 population-based controls using single, spot urine samples collected after disease diagnosis in cases. Total urinary BPA concentration (free and conjugated species) was quantified using a high-performance liquid chromatography-mass spectrometry method. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for urinary creatinine concentrations, age and reference year. We also evaluated the association by disease subtypes, ovarian and non-ovarian pelvic endometriosis, that may be etiologically distinct. MAIN RESULTS AND THE ROLE OF CHANCE: We did not observe a statistically significant association between total urinary BPA concentrations and endometriosis overall. We did observe statistically significant positive associations when evaluating total urinary BPA concentrations in relation to non-ovarian pelvic endometriosis (second versus lowest quartile: OR 3.0; 95% CI: 1.2, 7.3; third versus lowest quartile: OR 3.0; 95% CI: 1.1, 7.6), but not in relation to ovarian endometriosis. LIMITATIONS, REASONS FOR CAUTION: Given the short elimination half-life of BPA, our study was limited by the timing of collection of the single urine sample, that occurred after case diagnosis. Thus, our BPA measurements may not accurately represent the participants' levels during the etiologically relevant time period for endometriosis development. In addition, since it was not feasible in this population-based study to surgically confirm the absence of disease, it is possible that some controls may have had undiagnosed endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: By using population-based data, it is more likely that the controls represented the underlying frequency of BPA exposure in contrast to prior studies that used for comparison control women undergoing surgical evaluation, where the indication for surgery may be associated with BPA exposure. The significant associations observed in this study suggest that BPA may affect the normal dynamic structural changes of hormonally responsive endometrial tissue during the menstrual cycle, promoting the establishment and persistence of refluxed endometrial tissue in cases with non-ovarian pelvic endometriosis. Further research is warranted to confirm our novel findings in endometriosis subtypes that may be etiologically distinct. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Institutes of Health, National Institute of Environmental Health Sciences (grant number R03 ES019976), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant number R01 HD033792); US Environmental Protection Agency, Science to Achieve Results (STAR) (grant number R82943-01-0) and National Institute of Nursing Research (grant number F31NR013092) to KU for training support. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, National Institute of Nursing Research or the National Institutes of Health. The authors have no actual or potential competing financial interests. TRIAL REGISTRATION NUMBER: Not applicable.

Intimate partner violence and neighborhood income: a longitudinal analysis.

This investigation used a longitudinal design to examine the relationship between neighborhood-level income, individual-level predictors, and police-reported intimate partner violence in 5,994 urban couples followed over 2 years. At the baseline abuse incident, intimate partner violence rates were highest in the poorest neighborhoods (13.8 per 1,000 women in the lowest income quartile, followed by 12.1, 8.2, and 5.0 in the respective higher income quartiles). However, in the longitudinal analysis, weapon use at the baseline abuse event was a much stronger predictor of repeat abuse (incident rate ratios ranging from 1.72 for physical abuse to 1.83 for non-physical abuse) than neighborhood income.

Placenta accreta and maternal morbidity in the Republic of Ireland, 2005-2010.

OBJECTIVE: To describe the nationwide prevalence of placenta accreta and to quantify its impact on maternal morbidity. METHODS: Using discharge data for public hospitals in Ireland, years 2005-2010, deliveries with placenta accreta were identified using ICD-10-AM code for morbidly adherent placenta and compared with deliveries without the condition. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Placenta accreta prevalence increased 34% from 2005 to 2010 (7.9/10 000 deliveries versus 10.6/10 000 deliveries). This condition was associated with a substantial increased risk of hemorrhage (aOR: 16.6, 95% CI: 13.4-20.5), hysterectomy (aOR: 950.6, 95% CI: 632.9-1427.9), procedures to reduce uterine blood flow (aOR: 72.4, 95% CI: 35.1-149.4), transfusion (aOR: 41.8, 95% CI: 33.4-52.2), anemia (aOR 15.1, 95% CI: 10.8-21.0), abdominal organ injury (aOR: 8.2, 95% CI: 5.2-13.1), bladder surgery (aOR: 38.5, 95% CI: 21.8-68.1), mechanical ventilation (aOR: 63.2, 95% CI: 28.4-140.6), intensive care unit admission (aOR: 41.3, 95% CI: 30.0-56.9), and co-existing placenta previa (aOR: 23.2, 95% CI: 16.8-31.8) as well as increased risk of cesarean section, longer hospitalization and stillbirth. CONCLUSIONS: To our knowledge, this is the first study to use a comparison group of deliveries without placenta accreta and quantitatively illustrate with odds ratios the profound adverse health effects of this condition on the mother.

Organochlorine pesticides and risk of endometriosis: findings from a population-based case-control study.

BACKGROUND: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. OBJECTIVE: We investigated endometriosis risk in relation to environmental exposure to OCPs. METHODS: We conducted the present analyses using data from the Women's Risk of Endometriosis (WREN) study, a population-based case-control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. RESULTS: Our data suggested increased endometriosis risk associated with serum concentrations of ß-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum ß-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). CONCLUSIONS: In our case-control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of ß-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women.

Phthalates and risk of endometriosis.

BACKGROUND: Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. OBJECTIVE: To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. METHODS: We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. RESULTS: The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. CONCLUSIONS: Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

Genetic variation in the sex hormone metabolic pathway and endometriosis risk: an evaluation of candidate genes.

OBJECTIVE: To evaluate the relationship between common genetic variation in genes involved in the biosynthesis and signaling of estrogen and progesterone and endometriosis risk. DESIGN: Genetic polymorphism analysis. SETTING: Population-based case-control study conducted in Group Health Cooperative enrollees in western Washington. PATIENT(S): Women with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001 (n = 256) and age- and reference year-matched female control subjects without a history of endometriosis (n = 567). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): We evaluated the relationship between common genetic variation and endometriosis risk, using gene-based tests and single-variant analysis of genetic polymorphisms in ESR1, ESR2, PGR, CYP17A1, CYP19A1, HSD17B1, HSD17B2, CYP1A1, CYP1A2, COMT, and GSTM1. RESULT(S): The most consistent gene-based association with endometriosis risk was for CYP19A1. We did not find evidence for consistent significant associations between previously reported candidate SNPs in sex hormone-related genes and endometriosis risk. CONCLUSION(S): In summary, we report increased endometriosis risk with CYP19A1 gene-based tests; replication of the association between endometriosis and this gene or gene region is necessary in a larger study population.

Population-based ectopic pregnancy trends, 1993-2007.

BACKGROUND: The accuracy of ectopic pregnancy rates based on nationally representative data has been compromised for many years, impairing surveillance and evaluation of the continued public health importance of this condition. PURPOSE: To estimate long-term population-based ectopic pregnancy rates and trends within a defined population over a largely unevaluated time period, including the evaluation of trends in outpatient versus inpatient management and medical versus surgical treatment modalities. METHODS: Using computerized Group Health Cooperative inpatient and outpatient data, age-adjusted and age-specific ectopic pregnancy rates were calculated from 1993 to 2007 among enrollees aged 15-44 years. Overall trends and trends for care setting (inpatient versus outpatient) and treatment modality (medical versus surgical) were also evaluated. Analyses were conducted in 2009. RESULTS: Between 1993 and 2007, a total of 2114 ectopic pregnancy cases (726 inpatient; 1388 outpatient) were identified among 1,180,070 woman-years, an annual age-adjusted ectopic pregnancy rate of 17.9 per 10,000 woman-years. Rates were stable from 1993 to 2004 and increased in the most recent 3 years (2005-2007, rate=21.1 per 10,000 woman-years). Rates per 1000 pregnancies increased over the 15-year period from 19.2 to 26.2 per 1000 pregnancies (p-value=0.001). Inpatient-diagnosed cases decreased from 45.4% in 1993-1995 to 26.9% in 2005-2007 (p-value<0.0001) and the percentage with surgical treatment decreased from 48.1% to 30.7% (p-value<0.0001). CONCLUSIONS: The results suggest a trend toward increasing ectopic pregnancy rates over a recent 15-year period. Rates are similar to the last available national estimate, suggesting that the significance of ectopic pregnancy as a public health problem has not diminished in these intervening years.

A case-control investigation of adenomyosis: impact of control group selection on risk factor strength.

OBJECTIVE: Using a medical record abstraction-based case-control study with two control groups, we evaluated adenomyosis risk factors and investigated differences related to comparison group selection. MATERIALS AND METHODS: Medical records of all female 18- to 49-year-old Group Health (GH) enrollees with ICD-9 code 617.0 were abstracted using a standard data collection form. Cases were enrollees diagnosed with adenomyosis (n = 174) between April 1996 and September 2001. For comparison, medical records of two control groups were selected from the GH population: An age-matched sample of female enrollees (population-based controls; n = 149) and all female 18- to 49-year-old enrollees undergoing a hysterectomy (hysterectomy controls; n = 106) during the same time without adenomyosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression, adjusted for identified covariates. RESULTS: Compared with normal and underweight women, overweight and obese women had increased adenomyosis risk using hysterectomy controls (OR, 2.2, 95% CI, 1.0-4.5; obese: OR, 2.2; 95% CI, 1.1-4.3) and population controls (overweight: OR, 2.1; 95% CI, 1.2-4.0; obese: OR, 3.8; 95% CI, 2.0-7.0). Using population controls, women with at least one live birth were more likely to have adenomyosis than nulliparous women (OR, 3.4; 95% CI, 1.9-6.2). CONCLUSION: Although some risk factors persisted in analyses using either control group, divergent results in relation to other risk factors for adenomyosis suggest that results of investigations of this disease may be affected by the choice of the comparison population.

Associations between polymorphisms in glucuronidation and sulfation enzymes and sex steroid concentrations in premenopausal women in the United States.

Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGT) and sulfation, catalyzed by sulfotransferases (SULT), are pathways through which sex steroids are metabolized to less active compounds. These enzymes are highly polymorphic and genetic variants frequently result in higher or lower activity. The phenotypic effects of these polymorphisms on circulating sex steroids in premenopausal women have not yet been investigated. One hundred and seventy women aged 40-45 years had a blood sample drawn during the follicular phase of the menstrual cycle for sex steroid measures and to obtain genomic DNA. Urine was collected for 2-hydroxy (OH) estrone (E(1)) and 16α-OH E(1) measures. Generalized linear regression models were used to assess associations between sex steroids and polymorphisms in the UGT1A and UGT2B families, SULT1A1, and SULT1E1. Women with the UGT1A1(TA7/TA7) genotype had 25% lower mean estradiol (E(2)) concentrations compared to the wildtype (TA6/TA6) (p=0.02). Similar associations were observed between SULT1A1(R213/H213) and E(1) (13% lower mean E(1) concentration vs. wildtype; p-value=0.02) and UGT2B4(E458/E458) and dehydroepiandrosterone (DHEA) (20% lower mean DHEA vs. wildtype; p-value=0.03). The SULT1E1(A/C) and the UGT1A1(TA7)-UGT1A3(R11) haplotypes were associated with reduced estrogen concentrations. Further study of UGT and SULT polymorphisms and circulating sex steroid measures in larger populations of premenopausal women is warranted.

Diet and risk of endometriosis in a population-based case-control study.

Diet plausibly has a role in the aetiology of endometriosis through effects on steroid hormone levels; however, few published studies have examined the diet and endometriosis risk. We evaluated dietary risk factors for endometriosis in a population-based case-control study. Cases were 284 Group Health (GH) enrollees aged 18-49 years with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001. Controls were 660 randomly selected age-matched female GH enrollees without a history of endometriosis. Nutrients and selected food groups were assessed using the Women's Health Initiative FFQ. OR of endometriosis risk associated with dietary exposures were estimated using unconditional logistic regression and adjusted for identified covariates. Increased total fat consumption was associated with decreased endometriosis risk (fourth quartile v. lowest: OR 0·5, 95% CI 0·2, 1·0, P-trend = 0·12). Increased ß-carotene consumption and servings/d of fruit were associated with increased risk (ß-carotene third quartile v. lowest: OR 1·7, 95% CI 1·1, 2·6; fourth quartile v. lowest: OR 1·6, 95% CI 1·0, 2·5, P-trend 0·16; fruit >2 servings/d v. < 1: OR 1·5, 95% CI 1·0, 2·3, P-trend = 0·04). We also found a suggestion of decreased endometriosis risk associated with the consumption of dairy products (2 servings/d v. ≤ 1: OR 0·6, >2 servings/d v. ≤ 1: OR 0·7), but this association was not statistically significant for the highest tertile. The present study suggests that specific dietary components may be associated with endometriosis risk.

Intimate partner survivors' help-seeking and protection efforts: a person-oriented analysis.

Domestic violence advocates and researchers advocate for a survivor-centered approach for assisting women experiencing intimate partner violence (IPV), with individualized safety plans and services; yet little empirical work has been done to determine IPV survivors' specific combinations of vulnerabilities and assets that might inform such an approach. Using latent profile analysis of a cohort of 448 survivors, five distinct subgroups were previously identified in terms of biopsychosocial asset and vulnerability profiles. The purpose of the current study was to apply person-oriented methodology for survivor-centered investigation of differences in help-seeking and protective actions according to subgroup membership within this cohort. Though not differing demographically, the subgroups were found to differ significantly and meaningfully in their patterns of IPV help-seeking and protective actions. Thus, reliance on population-aggregate linear relationships between IPV exposure and safety efforts may risk overlooking important variation by vulnerability and asset profile, and knowledge of distinct clusters among functioning profiles may help with understanding of survivors' coping strategies.The authors outline service-need considerations across the subgroups and provide guidance for targeted outreach, locating IPV survivors and matching services to their needs.

Non-dioxin-like polychlorinated biphenyls and risk of endometriosis.

BACKGROUND: Endometriosis, a gynecologic disorder affecting 8-10% of reproductive-age women in the United States, is defined as the presence of endometrial tissue outside the uterus and is linked to pelvic pain and infertility. Environmental contaminants, including polychlorinated biphenyls (PCBs), are hypothesized to contribute to endometriosis risk through effects on steroid hormones. OBJECTIVE: We evaluated serum concentrations of certain noncoplanar PCBs, which have no or only weak dioxin-like properties, as risk factors for endometriosis. METHODS: In a case-control study of Group Health enrollees in western Washington State, 20 PCB congeners were measured in serum from surgically confirmed endometriosis cases that were newly diagnosed between 1996 and 2001 (n = 251) and from female controls matched for age and reference year (n = 538). RESULTS: Summed and estrogenic PCB concentrations were not associated with endometriosis risk [summed: odds ratio (OR) = 1.3; 95% confidence interval (CI), 0.8-2.2; estrogenic: OR = 1.1; 95% CI, 0.8-1.4]. Although several congener-specific ORs were statistically above or below the null (PCB 170: third quartile vs. lowest: OR = 0.5; 95% CI, 0.3-0.9; PCB 196: third quartile vs. lowest: OR = 0.4; 95% CI, 0.2-0.7; PCB 201: second vs. lowest: OR = 0.5; 95% CI, 0.3-0.8; third quartile vs. lowest: OR = 0.4; 95% CI, 0.2-0.7), there were no overall consistent patterns of endometriosis risk. CONCLUSIONS: Taken in context with other North American studies, our findings suggest that noncoplanar PCB concentrations consistent within the range of exposure currently observed in western Washington State do not contribute meaningfully to endometriosis risk.

Physical activity, physical exertion, and miscarriage risk in women textile workers in Shanghai, China.

BACKGROUND: Strenuous occupational physical activity and physical demands may be risk factors for adverse reproductive outcomes. METHODS: A retrospective study in the Shanghai, China textile industry study collected women's self-reported reproductive history. Occupational physical activity assessment linked complete work history data to an industry-specific job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression for the first pregnancy outcome and utilized generalized estimating equations to consider all pregnancies per woman. RESULTS: Compared with women employed in sedentary jobs, a reduced risk of miscarriage was found for women working in jobs with either light (OR 0.18, 95% CI: 0.07, 0.50) or medium (OR 0.24, 95% CI: 0.08, 0.66) physical activity during the first pregnancy and over all pregnancies (light OR 0.32, 95% CI: 0.17, 0.61; medium OR 0.43, 95% CI: 0.23, 0.80). Frequent crouching was associated with elevated risk (OR 1.82, 95% CI: 1.14, 2.93; all pregnancies per woman). CONCLUSIONS: Light/medium occupational physical activity may have reduced miscarriage risk, while specific occupational characteristics such as crouching may have increased risk in this cohort.