Kathleen Paul

Agricultural-related chemical exposures, season of conception, and risk of gastroschisis in Washington State.

OBJECTIVE We sought to determine if periconceptional exposure to agrichemicals was associated with the development of gastroschisis. STUDY DESIGN We conducted a retrospective, case-controlled study using Washington State Birth Certificate and US Geological Survey databases. Cases included all live-born singleton infants with gastroschisis. Distance between a womans residence and site of elevated exposure to agrichemicals was calculated. Multivariate regression was used to estimate the association between surface water concentrations of agrichemicals and the risk of gastroschisis. RESULTS Eight hundred five cases and 3616 control subjects were identified. Gastroschisis occurred more frequently among those who resided <25 km from a site of high atrazine concentration (odds ratio, 1.6). Risk was related inversely to the distance between the maternal residence and the closest toxic atrazine site. In multivariate analysis, nulliparity, tobacco use, and spring conception remained significant predictive factors for gastroschisis. CONCLUSION Maternal exposure to surface water atrazine is associated with fetal gastroschisis, particularly in spring conceptions.

Labor induction with a foley balloon inflated to 30 mL compared with 60 mL: A randomized controlled trial

OBJECTIVE: To compare 30-mL and 60-mL Foley balloon inflation for labor induction and the effect on length of labor and mode of delivery. METHODS: Women with term, vertex, singleton pregnancies (n=192) and a Bishop score less than 5 were assigned randomly to receive a transcervical Foley balloon inflated to either 30 mL or 60 mL. Exclusion criteria were painful, regular contractions on admission, ruptured membranes, low-lying placenta, or prior hysterotomy. Randomization was stratified by parity, and health care providers were blinded to Foley balloon size. Primary outcome was delivery within 24 hours of Foley balloon placement. Secondary outcomes included delivery within 12 hours, time from Foley balloon placement to expulsion, cervical dilation after Foley balloon expulsion, maximum oxytocin dose, method of delivery, chorioamnionitis, meconium, cervical laceration, abruption, 5-minute Apgar score, and umbilical cord gases. RESULTS: A higher proportion of women randomly assigned to the 60-mL Foley balloon achieved delivery within 12 hours of placement compared with the 30-mL Foley balloon group (26% compared with 14%, P=.04). This difference was more pronounced among nulliparous women. There was no difference in median time interval to delivery or proportion of women who achieved delivery within 24 hours. Median cervical dilation after Foley balloon expulsion was higher in the 60-mL Foley balloon group (4 cm compared with 3 cm, P<.01). There were no differences in the frequencies of cesarean delivery, maternal morbidity, or neonatal outcomes. CONCLUSION: Labor induction using Foley balloons inflated to 60 mL was more likely to achieve delivery within 12 hours compared with 30-mL inflation. There were no differences in delivery within 24 hours, cesarean delivery, labor complications, or neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00451308. LEVEL OF EVIDENCE: I

Inadequate prenatal care and risk of preterm delivery among adolescents: a retrospective study over 10 years

OBJECTIVE The aim of this study was to determine whether inadequate prenatal care is associated with increased risk of preterm birth among adolescents. STUDY DESIGN We selected a random sample of women under age 20 years with singleton pregnancies delivering in Washington State between 1995 and 2006. Multivariate logistic regression was used to assess the association between prenatal care adequacy (percent of expected visits attended, adjusted for gestational age) and preterm birth. RESULTS Of 30,000 subjects, 27,107 (90%) had complete data. Women without prenatal care had more than 7-fold higher risk of preterm birth (n = 84 [24.1%]; adjusted odds ratio [aOR], 7.4), compared with those attending 75-100% of recommended visits (n = 346 [3.9%]). Women with less than 25%, 25-49%, or 50-74% of expected prenatal visits were at significantly increased risk of preterm birth; risk decreased linearly as prenatal care increased (n = 60 [9.5%], 132 (5.9%], 288 [5%]; and aOR, 2.5, 1.5, and 1.3, respectively). CONCLUSION Inadequate prenatal care is strongly associated with preterm birth among adolescents.

Correlates of cervical Mycoplasma genitalium and risk of preterm birth among Peruvian women.

Background: Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease in nonpregnant women. We investigated associations between cervical M genitalium, demographic and behavioral risk factors for sexually transmitted infection and preterm birth among low-income Peruvian women. Methods: This case-control study, conducted at the Instituto Nacional Materno Perinatal, Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and 667 controls who delivered at ≥37 weeks. Within 48 hours after delivery, subjects underwent interviews, medical record review, and collection of cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by culture. Odds ratios and 95% confidence intervals were calculated for associations between M. genitalium, other genital infections and risk factors, and preterm birth. Multivariable logistic regression was used to adjust for potential confounders. Results: Cervical M. genitalium was detected in 3% of subjects and was significantly associated with C. trachomatis infection (P < 0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence interval: 1.2–5.0, P = 0.014), and marginally associated with T. vaginalis (P = 0.05). M. genitalium detection was also associated with younger maternal age (P = 0.003) but not with other risk factors for preterm birth. The association between cervical M. genitalium detection and preterm birth remained significant after adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis. Conclusions: Cervical M. genitalium detection was independently associated with younger maternal age and preterm birth, suggesting that this organism may be an infectious correlate of spontaneous preterm birth.

Cervicovaginal Shedding of HIV Type 1 Is Related to Genital Tract Inflammation Independent of Changes in Vaginal Microbiota

We examined the relationship of proinflammatory vaginal cytokines and secretory leukocyte protease inhibitor (SLPI) with genital HIV-1 shedding after controlling for genital coinfections. Fifty-seven HIV-1-infected women in Seattle, WA (n = 38) and Rochester, NY (n = 19) were followed every 3-4 months for a total of 391 visits. At each visit, plasma and cervicovaginal lavage (CVL) were tested for HIV-1 RNA using qPCR. Vaginal samples were tested for bacterial vaginosis, yeast, hydrogen peroxide-producing Lactobacillus colonization, Trichomonas vaginalis, Neisseria gonorrhea, Chlamydia trachomatis, CMV, and HSV shedding. CVL interleukins (IL)-1β, IL-6, IL-8, and SLPI were measured using ELISA. Linear regression with generalized estimating equations examined effects of cytokine concentrations on CVL HIV-1 RNA, adjusted for plasma HIV RNA, and measured coinfections. CVL IL-1β and IL-8 were significantly associated with CVL HIV-1 RNA. This persisted after adjusting for plasma HIV-1 RNA. Higher levels of IL-1β were associated with higher concentrations of HIV-1 RNA in CVL (β = 0.25, 95% CI 0.09, 0.42), as were higher levels of IL-8 (β = 0.34, 95% CI 0.17, 0.50). Adjusting for the presence of the coinfections described, this relationship was attenuated for IL-1β (β = 0.16; 95% CI -0.01, 0.33) but still significant for IL-8 (β = 0.29; 95% CI 0.13, 0.45). The proinflammatory cytokines IL-1β and IL-8 are associated with higher cervicovaginal HIV-1 RNA concentrations, even after controlling for plasma viral load and vaginal microbial cofactors. This association suggests that there may be additional, noninfectious causes of inflammation that increase cervicovaginal HIV-1 shedding.

The Relationship between Racial Identity, Income, Stress and C-Reactive Protein among Parous Women: Implications for Preterm Birth Disparity Research

The persistent racial disparity in preterm birth (PTB)remains one of the most obvious yet poorly understood health disparities in the United States, and current evidence suggests that maternal stress, infection and inflammation may play an important role in the etiology of PTB. In this context, we assessed the complex relationships among racial identity; socioeconomic status (SES); psychosocial factors; and serum C-reactive protein (CRP), an inflammatory biomarker, among parous women in King County, WA. African-American women consistently reported a higher number of stressful life events than white American women (4.6 vs. 2.9, p < 0.001), as well as slightly higher levels of perceived stress and lower social support (24.7 vs. 22.2, p = 0.011, and 3.4 vs. 3.6, p = 0.06, respectively). In the multivariate analysis, African-American race, low-income status and their interaction were all independently associated with CRP; when further adjusted for proximal psychosocial, behavioral and infectious factors, race and income associations were significantly reduced. Stressful life events score was the single best proximal predictor of CRP levels (beta = 0.07 per event,p < 0.001), while perceived stress and social support were not significantly related to CRP. These results support the hypothesis that differences in CRP by racial identity and income may be mediated by differences in proximal risk factors, including stressful life events and health behaviors such as smoking. Objective life event stressors may be important to consider in future studies investigating a potential inflammatory etiology for preterm birth.

Estimating Volume of Cervicovaginal Secretions in Cervicovaginal Lavage Fluid Collected for Measurement of Genital HIV-1 RNA Levels in Women

ABSTRACT To assess the volume of genital fluid collected for measuring the HIV-1 RNA level in cervicovaginal fluid, phosphate-buffered saline containing 10 mM LiCl was used. Thirty-eight women provided 275 cervicovaginal specimens. The estimated median volume of cervicovaginal fluid was 0.51 ml (interquartile range, 0.33, 0.69).

A Summary of Preclinical Topical Microbicide Rectal Safety and Efficacy Evaluations in a Pigtailed Macaque Model

Background: There is widespread recognition of the potential promise of vaginal microbicides as a tool to combat global human immunodeficiency virus/acquired immunodeficiency syndrome and sexually transmitted infections epidemics, and candidate product development has maintained a rapid pace in recent years; however, rectal microbicide development has received less attention. As it is likely that commercial products developed for vaginal use will also be used rectally, there is a clear need to assess the safety and efficacy of candidate microbicide products specifically in the rectal compartment. Methods: We have developed a standardized protocol for preclinical rectal safety and (chlamydial) efficacy assessment of topical microbicide candidates in a nonhuman primate model. We evaluated a total of 12 test compounds for rectal safety (via rectal pH, microflora, and rectal lavage) and 1 compound for efficacy against rectal chlamydial infection. Results: In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the rectal environment. We also outline the specific criteria used to recommend products move into preclinical rectal efficacy trials or be recommended for reformulation to the product developer. In summary, we observed significant adverse effects in 2 products. The single product that underwent efficacy evaluation was not observed to be protective against rectal chlamydial infection. Conclusions: A preclinical safety and efficacy model is critical to promoting rectal microbicide development, which will ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.

The vaginal microflora in relation to gingivitis

BackgroundGingivitis has been linked to adverse pregnancy outcome (APO). Bacterial vaginosis (BV) has been associated with APO. We assessed if bacterial counts in BV is associated with gingivitis suggesting a systemic infectious susceptibilty.MethodsVaginal samples were collected from 180 women (mean age 29.4 years, SD ± 6.8, range: 18 to 46), and at least six months after delivery, and assessed by semi-quantitative DNA-DNA checkerboard hybridization assay (74 bacterial species). BV was defined by Gram stain (Nugent criteria). Gingivitis was defined as bleeding on probing at ≥ 20% of tooth sites.ResultsA Nugent score of 0–3 (normal vaginal microflora) was found in 83 women (46.1%), and a score of > 7 (BV) in 49 women (27.2%). Gingivitis was diagnosed in 114 women (63.3%). Women with a diagnosis of BV were more likely to have gingivitis (p = 0.01). Independent of gingival conditions, vaginal bacterial counts were higher (p < 0.001) for 38/74 species in BV+ in comparison to BV- women. Counts of four lactobacilli species were higher in BV- women (p < 0.001). Independent of BV diagnosis, women with gingivitis had higher counts of Prevotella bivia (p < 0.001), and Prevotella disiens (p < 0.001). P. bivia, P. disiens, M. curtisii and M. mulieris (all at the p < 0.01 level) were found at higher levels in the BV+/G+ group than in the BV+/G- group. The sum of bacterial load (74 species) was higher in the BV+/G+ group than in the BV+/G- group (p < 0.05). The highest odds ratio for the presence of bacteria in vaginal samples (> 1.0 × 104 cells) and a diagnosis of gingivitis was 3.9 for P. bivia (95% CI 1.5–5.7, p < 0.001) and 3.6 for P. disiens (95%CI: 1.8–7.5, p < 0.001), and a diagnosis of BV for P. bivia (odds ratio: 5.3, 95%CI: 2.6 to 10.4, p < 0.001) and P. disiens (odds ratio: 4.4, 95% CI: 2.2 to 8.8, p < 0.001).ConclusionHigher vaginal bacterial counts can be found in women with BV and gingivitis in comparison to women with BV but not gingivitis. P. bivia and P. disiens may be of specific significance in a relationship between vaginal and gingival infections.

A Summary of Preclinical Topical Microbicide Vaginal Safety and Chlamydial Efficacy Evaluations in a Pigtailed Macaque Model

Background: The development of topical microbicides represents a new and exciting field in the prevention of sexually transmitted diseases, and it is especially important that candidate products undergo rigorous preclinical safety and efficacy testing before advancing to clinical trials. Methods: We have developed a standardized protocol for preclinical vaginal safety and efficacy assessment of topical microbicide candidates in a nonhuman primate model. Over 7 years of funding under an NIH contract, we evaluated a total of 28 test compounds for vaginal safety (via colposcopy, vaginal pH, and microflora) and 9 compounds for efficacy against cervical chlamydial infection. In this article, we describe our methods in detail and summarize our results, particularly noting the ability of our model to distinguish products with deleterious effects on the cervicovaginal environment. We also outline the specific criteria used to determine which products should move into efficacy trials and which should be recommended for reformulation to the manufacturer. Results: Overall, we noted acceptable safety profiles for 24 of 28 candidate products. Common findings included a transient decrease in vaginal pH, petechiae, and mild erythema. Four products were associated with significant adverse colposcopic findings including blisters, epithelial abrasions, and friability; all 4 products were successfully reformulated and showed acceptable safety profiles at lower concentrations. No products showed complete protection against cervical chlamydial infection. Conclusions: The macaque preclinical safety and efficacy model is critical to maintaining the pace of topical microbicide development, which could ultimately offer a significant opportunity for intervention in the global HIV/AIDS epidemic.