Impact of Quitline Services on Tobacco Cessation: An Application of Modern Epidemiological Methods.

This study investigated the effectiveness of quitline service intensity (high vs. low) on past 30-day tobacco abstinence at 7-months follow-up, using observational data from the Oklahoma Tobacco Helpline (OTH) between April 2020 and December 2021. To assess the impact of loss to follow-up and non-random treatment assignment, we fit the parameters of a marginal structural model to estimate inverse probability weights for censoring (IPCW) and treatment (IPTW) and combined (IPCTW). The Risk Ratio (RR) was estimated using modified Poisson regression with robust variance estimator. Of the 4,695 individuals included in the study, 64% received high-intensity cessation services, and 53% were lost to follow-up. Using the conventional complete case analysis (responders only), high-intensity cessation services were associated with abstinence (RR=1.18; 95 CI: 1.04, 1.34). The effect estimate was attenuated after accounting for censoring (RR=1.14; 95% CI: 1.00, 1.30). After adjusting for both baseline confounding and selection bias via IPTCW, high-intensity cessation services were associated with 1.23 times (95% CI: 1.08, 1.41) the probability of abstinence compared to low-intensity services. Despite relatively high loss to follow-up, accounting for selection bias and confounding did not notably impact quit rates or the relationship between intensity of quitline services and tobacco cessation among OTH participants.

Cannabis Use and Subsequent CIGARETTE Discontinuation among U.S. Adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1-5.

INTRODUCTION: This study examined the association between current co-use of cannabis and cigarettes in the past 30 days, and subsequent cigarette discontinuation (past 30-day point prevalence abstinence) among U.S. adults with established cigarette use in the Population Assessment of Tobacco and Health (PATH) Study. Additionally, we investigated the impact of co-use on the subsequent discontinuation of all combustible tobacco products. METHODS: A total of 26,381 observations contributed by 8,218 adults with established cigarette use (i.e., smoked ≥ 100 cigarettes in their lifetime, and currently smoking cigarettes every day or some days) from Waves 1-5 of the PATH Study were included in the analysis. Weighted Generalized Estimating Equations (GEE) models were used to evaluate the association between current co-use at baseline (Waves 1-4) with the outcomes assessed at the subsequent wave (cigarette and combustible tobacco discontinuation at Waves 2-5). Final models included: demographic characteristics (age, sex, race and ethnicity, educational attainment), behavior characteristics (intention to quit, internalizing symptoms, externalizing symptoms, substance use problems), and wave-pair. RESULTS: Over one-third (35.91%) of cigarette users self-reported co-use during the study period. Cannabis use among adults with established cigarette use increased over time. Co-use was associated with a decreased odds of cigarette smoking discontinuation at follow-up, after adjusting for covariates (aOR: 0.81; 95% CI: 0.72, 0.93; p=0.0018). Similar effect sizes were observed for discontinuation of all combustible tobacco products (aOR: 0.75; 95% CI: 0.65, 0.86; p<.0001). CONCLUSIONS: Cannabis use among adults who smoke cigarettes was inversely related to subsequent cigarette discontinuation, suggesting that co-use may reduce likelihood of successful tobacco cessation. IMPLICATIONS: Findings demonstrate that cannabis use may lead to lower odds of discontinuation among adults with established cigarette use; therefore, individuals that co-use cigarettes and cannabis may need additional tobacco cessation support. Notably, this study observed an increase in co-use of cigarettes and cannabis, emphasizing the need for researchers and public health programs to shift their focus towards understanding and addressing concurrent substance use among adults who smoke cigarettes.

Exposure to persistent organic pollutants in newborn dried blood spots and childhood acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p'-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p'-DDE, ORs were significantly lower for those exposed to the highest tertile of p,'p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,'p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology.

Motivation toward vasectomy based on abortion law changes in Oklahoma.

INTRODUCTION: In May 2022, lawmakers in Oklahoma passed House Bill 4327, which outlawed abortion after fertilization. The governor signed the bill on May 25, 2022. It is uncertain whether these changes will motivate more men in Oklahoma to undergo vasectomy. MATERIALS AND METHODS: Males seeking vasectomy were informed of the study and asked to participate. Participants filled out a survey regarding their marital status, number of children, fertility treatment history, and their influences in making the decision to pursue vasectomy. We removed the identifying information from the survey. After collection, the data was imported to a database. Medical records were investigated to confirm patients underwent the procedure. RESULTS: Of the 126 participants, 116 underwent vasectomy. Patients who did not undergo vasectomy tended to be older (38.4 vs. 34.2, p = 0.03). Participants who underwent vasectomy and were concerned about abortion laws tended to be married (69.7 vs. 30.3%, p = 0.04) with fewer children (1.2 vs. 2.3, p < 0.0001). When correlating specifically "concern about abortion laws" and going through with vasectomy, the risk ratio of 1.12 (95% CI 1.04, 1.20) indicates that patients concerned about abortion laws were slightly more likely to undergo vasectomy. CONCLUSIONS: Over 26% of men said that their decisions were somewhat impacted by abortion law changes. The concern about abortion law changes seemed to be predictive of patients undergoing vasectomy. Continued data collection will help determine whether there is a time-sensitive nature regarding the impact of abortion law changes on motivation to vasectomy.

HPV vaccination coverage and factors among American Indians in Cherokee Nation.

PURPOSE: We estimated human papillomavirus (HPV) vaccine initiation coverage among American Indian adolescents and identified factors associated with HPV vaccination among parents of these adolescents. METHODS: We developed, tested, and disseminated a survey to a random sample of 2,000 parents of American Indian adolescents aged 9-17 years who had accessed Cherokee Nation Health Services from January 2019 to August 2020. We used log-binomial regression to estimate the unadjusted and adjusted weighted prevalence proportion ratios (PPR) and 95% confidence intervals (CI) for adolescent HPV vaccine initiation. RESULTS: HPV vaccine initiation coverage (≥ 1 dose) was 70.7% among adolescents aged 13-17 years. The prevalence of HPV vaccine initiation was higher among American Indian adolescents whose parents were aware of the HPV vaccine (adjusted weighted PPR 3.41; 95% CI 2.80, 4.15) and whose parents received a recommendation from their provider (adjusted weighted PPR 2.70; 95% CI 2.56, 2.84). The most common reasons reported by parents to vaccinate their children were to protect them against HPV-associated cancers (25.7%) and receiving a recommendation from a healthcare provider (25.0%). Parents cited vaccine safety concerns as the main reason for not getting their children vaccinated (33.2%). CONCLUSIONS: HPV vaccine initiation coverage among American Indian adolescents in Cherokee Nation was consistent with the national survey estimates. However, allaying parental concerns about vaccine safety and encouraging providers to recommend the HPV vaccine could improve coverage.

Assessing urinary phenol and paraben mixtures in pregnant women with and without gestational diabetes mellitus: A case-control study.

Prior studies have identified the associations between environmental phenol and paraben exposures and increased risk of gestational diabetes mellitus (GDM), but no study addressed these exposures as mixtures. As methods have emerged to better assess exposures to multiple chemicals, our study aimed to apply Bayesian kernel machine regression (BKMR) to evaluate the association between phenol and paraben mixtures and GDM. This study included 64 GDM cases and 237 obstetric patient controls from the University of Oklahoma Medical Center. Mid-pregnancy spot urine samples were collected to quantify concentrations of bisphenol A (BPA), benzophenone-3, triclosan, 2,4-dichlorophenol, 2,5-dichlorophenol, butylparaben, methylparaben, and propylparaben. Multivariable logistic regression was used to evaluate the associations between individual chemical biomarkers and GDM while controlling for confounding. We used probit implementation of BKMR with hierarchical variable selection to estimate the mean difference in GDM probability for each component of the phenol and paraben mixtures while controlling for the correlation among the chemical biomarkers. When analyzing individual chemicals using logistic regression, benzophenone-3 was positively associated with GDM [adjusted odds ratio (aOR) per interquartile range (IQR) = 1.54, 95% confidence interval (CI) 1.15, 2.08], while BPA was negatively associated with GDM (aOR 0.61, 95% CI 0.37, 0.99). In probit-BKMR analysis, an increase in z-score transformed log urinary concentrations of benzophenone-3 from the 10th to 90th percentile was associated with an increase in the estimated difference in the probability of GDM (0.67, 95% Credible Interval 0.04, 1.30), holding other chemicals fixed at their medians. No associations were identified between other chemical biomarkers and GDM in the BKMR analyses. We observed that the association of BPA and GDM was attenuated when accounting for correlated phenols and parabens, suggesting the importance of addressing chemical mixtures in perinatal environmental exposure studies. Additional prospective investigations will increase the understanding of the relationship between benzophenone-3 exposure and GDM development.

Barriers and Factors Associated with HPV Vaccination Among American Indians and Alaska Natives: A Systematic Review.

American Indian and Alaska Native (AI/AN) persons bear a disproportionate burden of human papillomavirus (HPV)-associated cancers and face unique challenges to HPV vaccination. We undertook a systematic review to synthesize the available evidence on HPV vaccination barriers and factors among AI/AN persons in the United States. We searched fourteen bibliographic databases, four citation indexes, and six gray literature sources from July 2006 to January 2021. We did not restrict our search by study design, setting, or publication type. Two reviewers independently screened the titles and abstracts (stage 1) and full-text (stage 2) of studies for selection. Both reviewers then independently extracted data using a data extraction form and undertook quality appraisal and bias assessment using the modified Mixed Methods Appraisal Tool. We conducted thematic synthesis to generate descriptive themes. We included a total of 15 records after identifying 3017, screening 1415, retrieving 203, and assessing 41 records. A total of 21 unique barriers to HPV vaccination were reported across 15 themes at the individual (n = 12) and clinic or provider (n = 3) levels. At the individual level, the most common barriers to vaccination-safety and lack of knowledge about the HPV vaccine-were each reported in the highest number of studies (n = 9; 60%). The findings from this review signal the need to develop interventions that target AI/AN populations to increase the adoption and coverage of HPV vaccination. Failure to do so may widen disparities.

Platelet Counts during Pregnancy.

BACKGROUND: Platelet counts of less than 150,000 per cubic millimeter during uncomplicated pregnancies are described as gestational thrombocytopenia if no alternative cause is identified. Platelet counts may be even lower in women with pregnancy-related complications. However, the occurrence and severity of thrombocytopenia throughout pregnancy are not defined. METHODS: We evaluated platelet counts throughout pregnancy in women who delivered at Oklahoma University Medical Center between 2011 and 2014. These platelet counts were compared with those of nonpregnant women who were included in the National Health and Nutrition Examination Survey from 1999 through 2012. RESULTS: Among the 15,723 deliveries that occurred during the study period, 7351 women had sufficient data for our analyses. Of these women, 4568 had uncomplicated pregnancies, 2586 had pregnancy-related complications, and 197 had preexisting disorders associated with thrombocytopenia. Among the women who had uncomplicated pregnancies, the mean platelet count in the first trimester (mean gestation, 8.7 weeks) was 251,000 per cubic millimeter, which was lower than the mean platelet count in the 8885 nonpregnant women (273,000 per cubic millimeter) (P<0.001). At the time of delivery, 9.9% of the women with uncomplicated pregnancies had a platelet count below 150,000 per cubic millimeter. During the course of the uncomplicated pregnancies and deliveries, only 45 women (1.0%) had a platelet count below 100,000 per cubic millimeter. Among the 12 women with uncomplicated pregnancies who had a platelet count below 80,000 per cubic millimeter, only 5 (0.1%, among whom the range of platelet counts was 62,000 to 78,000 per cubic millimeter; median, 65,000) were identified by medical record review as having no alternative cause for the thrombocytopenia. Platelet counts of less than 150,000 per cubic millimeter at the time of delivery were more common among women who had pregnancy-related complications than among women who had uncomplicated pregnancies (11.9% vs. 9.9%, P=0.01). Throughout their pregnancies and deliveries, 59 women (2.3%) with pregnancy-related complications had a platelet count below 100,000 per cubic millimeter, and 31 (1.2%) had a platelet count below 80,000 per cubic millimeter. CONCLUSIONS: Mean platelet counts decreased during pregnancy in all the women, beginning in the first trimester. In women who have a platelet count of less than 100,000 per cubic millimeter, a cause other than pregnancy or its complications should be considered. (Funded by the National Heart, Lung, and Blood Institute.).

Metabolic syndrome in obesity: treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome.

BACKGROUND: Obesity is common in women with polycystic ovary syndrome. polycystic ovary syndrome and obesity are associated with reduced fertility. The effect of metabolic syndrome on the success of infertility treatment and pregnancy outcomes in women with polycystic ovary syndrome undergoing ovulation induction has not been investigated. OBJECTIVE: The objectives of this study were to determine the associations of metabolic syndrome on the rate of live birth after ovulation induction and pregnancy complications in obese women with polycystic ovary syndrome and determine whether there is a difference in outcomes concerning specific medications used for ovulation induction. STUDY DESIGN: This prospective cohort analysis used data collected from participants in the Pregnancy in Polycystic Ovary Syndrome II clinical trial conducted by the Reproductive Medicine Network. In the Pregnancy in Polycystic Ovary Syndrome II trial, 750 women with polycystic ovary syndrome and infertility were randomized to either clomiphene citrate or letrozole for ovulation induction for 1 to 5 cycles or until pregnancy occurred. Cox regression and modified Poisson regression, chi-square test, and Student t test or Wilcoxon test were used in this study. Outcomes of interest were rates of live birth and clinical pregnancy and pregnancy complications. Having metabolic syndrome was defined by the presence of at least 3 of 5 cardiometabolic risk factors (waist circumference of >88 cm, low high-density lipoprotein cholesterol of <50 mg/dL, triglycerides of ≥150 mg/dL, systolic blood pressure of ≥130 or diastolic blood pressure of ≥85 mm Hg, and fasting glucose of >100 mg/dL). In addition, we used a continuous metabolic syndrome z score. Body mass index categories were defined as normal (body mass index of <25 kg/m2), high (25 to 35 kg/m2), and very high (>35 kg/m2). RESULTS: As illustrated in the Table, early pregnancy losses showed no difference by metabolic syndrome. Fewer women achieved a clinical pregnancy (20.5% vs 29.7%; P=.007) or had a live birth (16.5% vs 27%; P=.001) in the presence of metabolic syndrome. Early pregnancy losses showed no difference by metabolic syndrome status. However, at least 1 pregnancy complication occurred more often with metabolic syndrome: 61.9% (26 of 42 cases) with metabolic syndrome vs 44.4% (59 of 133 cases) (P=.05) without metabolic syndrome. Gestational diabetes mellitus (35.7% vs 18.2%; P=.02) and macrosomia (21.4% vs 8.3%; P=.02) were more common in the presence of metabolic syndrome. After adjustment for other potential confounders, the rate ratio for live births for a 1-unit change in the metabolic syndrome z score was 0.89 (95% confidence interval, 0.79-1.00; P=.04) for those whose body mass index was 25 to 35 kg/m2. For the very high body mass index subgroup (>35 kg/m2), the independent effects of metabolic syndrome from obesity were harder to discern. The rate of live birth was higher with the use of letrozole, although metabolic syndrome had a different detrimental effect concerning the medication given. The overall incidence of pregnancy complications was high (approximately 49%) in the Pregnancy in Polycystic Ovary Syndrome II trial and the 2 medications. Letrozole was associated with more obstetrical complications in the presence of metabolic syndrome, and clomiphene was associated with a lower rate of live birth rate when metabolic syndrome was present. CONCLUSION: Metabolic syndrome is a risk factor that lowers the rate of live birth after ovulation for women with polycystic ovary syndrome, independent of obesity, and it is particularly associated with a lower rate of live birth for women using clomiphene compared with women using letrozole. In addition, metabolic syndrome is a risk factor for pregnancy complications for women with obesity using letrozole. Furthermore, having metabolic syndrome is a risk factor for gestational diabetes mellitus and macrosomia.

Clinical effectiveness of adding azithromycin to antimicrobial prophylaxis for cesarean delivery.

BACKGROUND: A recent large clinical trial demonstrated an approximately 50% decrease in the rate of postoperative infection in women who were laboring and/or had rupture of membranes for >4 hours and who received azithromycin in addition to standard preoperative antibiotic prophylaxis at the time of cesarean delivery. Given these results, our institution made a policy change in May 2017 to add azithromycin to standard preoperative prophylaxis for all cesarean deliveries. OBJECTIVE: This study aimed to evaluate the clinical effectiveness of adding azithromycin to preoperative antibiotic prophylaxis for cesarean delivery. STUDY DESIGN: We conducted a before-and-after cohort study of women delivered via cesarean delivery at our institution. The preimplementation group included women who delivered from March 1, 2016, to February 28, 2017, (before an institutional practice change of adding azithromycin to standard preoperative prophylaxis), and the postimplementation group included women who delivered from September 1, 2017, to August 31, 2018 (allowing a 6-month period for uptake of the practice change). The primary outcome was a composite of postoperative infections (endometritis, wound infection, other maternal infections). Unadjusted and adjusted risk ratios and 95% confidence intervals were estimated using a modified Poisson regression model. RESULTS: In the preimplementation (n=1171) and postimplementation (n=1168) groups, the incidence rates of the composite outcomes were 4.7% and 5.3%, respectively (P=.49). Both unadjusted (relative risk, 1.13; 95% confidence interval, 0.78-1.62) and adjusted (adjusted relative risk, 1.06; 95% confidence interval, 0.74-1.52) comparisons were not significantly different. In addition, results were statistically nonsignificant, but in the direction of lower rates of infection, in the after cohort for women in labor and/or with rupture of membranes for ≥4 hours (relative risk, 0.88 [95% confidence interval, 0.56-1.39]; adjusted relative risk, 0.82 [95% confidence interval, 0.52-1.30]) and for women with clinical chorioamnionitis (relative risk, 0.37 [95% confidence interval, 0.08-1.67]; data too sparse for adjusted analysis). In the subgroup of women who were not in labor, the after cohort had a statistically nonsignificant increased risk of the composite outcome in both unadjusted (relative risk, 1.53; 95% confidence interval, 0.86-2.72) and adjusted (adjusted relative risk, 1.48; 95% confidence interval, 0.83-2.65]) comparisons. CONCLUSION: In clinical practice, the addition of azithromycin to standard preoperative antibiotic prophylaxis for cesarean delivery may have an effect size smaller than seen in the large clinical trial prompting this practice change. Extrapolation of this regimen to women not in labor may be ineffective.

Controlled Release Dinoprostone Insert and Foley Compared to Foley Alone: A Randomized Pilot Trial.

OBJECTIVE: The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term. STUDY DESIGN: In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery. RESULTS: From April 2017 to January 2018, 100 women were randomized. Median (25-75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6-38.0) hours with DVI + Foley (n = 26) compared with 31.3 (23.3-46.9) hours with Foley (n = 24) (Wilcoxon p = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6-21.9) hours with DVI + Foley (n = 25) compared with 14.8 (12.7-19.5) hours with Foley (n = 25) (Wilcoxon p = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions. CONCLUSION: Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.

Infant sex differences in human milk intake and composition from 1- to 3-month post-delivery in a healthy United States cohort.

BACKGROUND: Macronutrient composition of human milk differs by infant sex, but few studies have examined sex differences in other milk components, or their potential modification by maternal body mass index (BMI). AIM: We compared milk intake and human milk hormone and cytokine concentrations at 1- and 3-month post-delivery and tested infant sex by maternal BMI (OW/OB vs. NW) interactions. SUBJECTS AND METHOD: Data were analysed for 346 mother-infant dyads in the Mothers and Infants Linked for Healthy Growth (MILk) Study at 1- and 3-month post-delivery. Infant milk intake was estimated by the change in infant weight after test feedings. Concentrations of glucose, insulin, leptin, adiponectin, interleukin-6 (IL-6), and C-reactive protein (CRP) were measured using ELISA. Multivariable linear regression and linear mixed models were used to estimate sex main effects and their interaction with maternal BMI. RESULTS: Mean glucose concentration at 1 month was 2.62 mg/dl higher for male infants, but no difference at 3 months was observed. Milk intake and concentrations for the other milk components were similar for males and females at both time points. Associations with infant sex did not differ significantly by maternal BMI. CONCLUSIONS: Among healthy United States mother-infant dyads, appetite, and growth-regulating factors in human milk did not differ significantly by infant sex.

Intrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial.

STUDY QUESTION: Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility? SUMMARY ANSWER: Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success. WHAT IS ALREADY KNOWN: We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome. STUDY DESIGN, SIZE, DURATION: This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%). LIMITATIONS, REASONS FOR CAUTION: This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI. WIDER IMPLICATIONS OF THE FINDINGS: Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI. STUDY FUNDING/COMPETING INTEREST(S): Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work. TRIAL REGISTRATION NUMBER: n/a.

The prevalence of infertility in American Indian/Alaska Natives and other racial/ethnic groups: National Survey of Family Growth.

BACKGROUND: The prevalence of infertility in American Indian/Alaska Native (AI/AN) populations is unknown. The objective of our study was to estimate the prevalence of infertility and impaired fecundity in the AI/AN population and other racial and ethnic groups. METHODS: We analyzed female respondent data from the pooled National Survey of Family Growth (NSFG) cycles 2002, 2006-2010, and 2011-2013. We used modified Poisson regression with robust error variance accounting for survey weighting to estimate prevalence proportion ratios (PPR) and 95% confidence intervals (CI) for NSFG definitions of infertility and impaired fecundity by race and Hispanic ethnicity. RESULTS: The prevalence of infertility and impaired fecundity in the pooled NSFG was 6.4% (95% CI 5.7, 7.0) and 11.0% (95% CI 11.0, 12.2), respectively. Compared to whites, blacks had a 1.45 times greater adjusted prevalence of infertility (95% CI 1.15, 1.83) and AI/ANs had a 1.37 times greater prevalence of infertility (95% CI 0.91, 2.06) compared to whites. We observed a 1.30 times greater prevalence of impaired fecundity among AI/AN (95% CI 1.04, 1.62) compared to whites. We observed no differences in impaired fecundity for black or Asian/Pacific Islander women compared to whites or for Hispanic compared to non-Hispanic women. CONCLUSIONS: Inequalities in the burden of reproductive impairments among blacks and AI/AN women warrant further evaluation to identify opportunities for prevention and disparity reduction.

Racial/Ethnic Differences in the Utilization of Infertility Services: A Focus on American Indian/Alaska Natives.

Objectives Previous studies have identified racial/ethnic disparities in infertility care, but patterns among American Indian/Alaska Natives (AI/AN) have not been reported. Our objective was to evaluate infertility services use in the US by race/ethnicity using data from the National Survey of Family Growth (NSFG). Methods We analyzed female respondent data from the pooled NSFG cycles 2002, 2006-2010 and 2011-2013. Respondents reported use of infertility services and types of services. We calculated weighted crude and adjusted prevalence proportion ratios (PPR) and 95% confidence intervals (95% CI) using modified Poisson regression with robust error variances accounting for the complex survey design to compare infertility services use across race/ethnicities. Results Overall, 8.7% of women reported using medical services to get pregnant. The prevalence of using any medical service to help get pregnant was lower for American Indian/Alaska Native (AI/AN) (PPR: 0.60, 95% CI 0.43-0.83) and black (PPR: 0.53, 95% CI 0.44-0.63) compared to white women and in Hispanic compared to non-Hispanic women (PPR: 0.57, 95% CI 0.48-0.67). The prevalence of accessing treatment, testing, and advice also differed by race and ethnicity. Conclusions for Practice We observed disparities in accessing services to get pregnant among AI/AN and black women and reduced use of advice among Asian/Pacific Islanders compared to whites. We also observed reduced service utilization for Hispanic compared to non-Hispanic women. Differential utilization of specific services suggests barriers to infertility care may contribute to reproductive health disparities among underserved populations.

Effect Modification of the Association Between Race and Stage at Colorectal Cancer Diagnosis by Socioeconomic Status.

OBJECTIVES: To compare risks of distant-stage colorectal cancer (CRC) diagnosis between whites and American Indian/Alaska Natives (AI/ANs) and to explore effect modification by area-based socioeconomic status (SES). DESIGN: Retrospective cohort study using data from the Oklahoma Central Cancer Registry. SETTING: Oklahoma. PARTICIPANTS: White and AI/AN cases of CRC diagnosed in Oklahoma between 2001 and 2008 (N = 8 438). A subanalysis was performed on the cohort of those aged 50 years and older (N = 7 728). MAIN OUTCOME MEASURE: Risk of distant-stage CRC diagnosis stratified by SES score. RESULTS: Race and SES were independently associated with distant-stage diagnosis. In SES-stratified analyses, AI/ANs in the 2 lowest SES groups experienced increased risks in the overall cohort and among those aged 50 years and older. In multivariable models, risks remained significant among those aged 50 years and older in the lowest SES groups (Adjusted risk ratio SES score of 2: 1.31, 95% confidence interval: 1.06-1.63 and adjusted risk ratio SES score of 1: 1.21, 95% confidence interval: 1.01-1.44). CONCLUSION: Socioeconomic status is an effect modifier in the association between race/ethnicity and stage at CRC diagnosis. Disparities in stage at CRC diagnosis exist between AI/ANs and whites with lower estimated SES. Efforts are needed to increase CRC screening among lower SES AI/ANs.

Association between benzene and congenital anomalies in Oklahoma, 1997-2009.

OBJECTIVES: Although the most common cause of death in infants, little is known about the aetiology of congenital anomalies. Recent studies have increasingly focused on environmental exposures, including benzene. While benzene is known to affect the central nervous system, the effects on the developing fetus are unclear. METHODS: We conducted a retrospective cohort study to evaluate the association between ambient benzene exposure and the prevalence of congenital anomalies among 628 121 singleton births in Oklahoma from 1997 to 2009. We obtained benzene from the Environmental Protection Agency's 2005 National-Scale Air Toxics Assessment for the census tract of the birth residence. We used modified Poisson regression with robust SEs to calculate prevalence proportion ratios (PPRs) and 95% CIs between quartiles of benzene exposure and critical congenital heart defects (CCHDs), neural tube defects (NTDs) and oral clefts adjusted for maternal education and tobacco use. RESULTS: Median benzene exposure concentration in Oklahoma was 0.57 µg/m3. We observed no association between benzene exposure and oral clefts, CCHDs or NTDs. When specific anomalies were examined, we observed an increased prevalence of cleft lip among those exposed to the second quartile of benzene compared with the first (PPR 1.50, 95% CI 1.05 to 2.13), though no association with higher levels of exposure. CONCLUSIONS: Our findings do not provide support for an increased prevalence of anomalies in areas more highly exposed to benzene. Future studies would benefit from pooling data from multiple states to increase statistical power and precision in studies of air pollutants and specific anomalies.

Platelet counts in women with normal pregnancies: A systematic review.

The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3,039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000-264,000/µL); second trimester, 238,000/µL (95% CI, 222,000-253,000/µL); third trimester, 224,000/µL (95% CI, 213,000-235,000/µL); delivery, 237,000/µL (95% CI, 209,000-264,000/µL); 4-8 weeks postpartum, 247,000/µL (95% CI, 207,000-287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross-sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy.

Benzene and childhood acute leukemia in Oklahoma.

BACKGROUND: Although childhood cancer is a leading cause of childhood mortality in the US, evidence regarding the etiology is lacking. The goal of this study was to evaluate the association between benzene, a known carcinogen, and childhood acute leukemia. METHODS: We conducted a case-control study including cases diagnosed with acute leukemia between 1997 and 2012 (n = 307) from the Oklahoma Central Cancer Registry and controls matched on week of birth from birth certificates (n = 1013). We used conditional logistic regression to evaluate the association between benzene, measured with the 2005 National-Scale Air Toxics Assessment (NATA) at census tract of the birth residence, and childhood acute leukemia. RESULTS: We observed no differences in benzene exposure overall between cases and controls. However, when stratified by year of birth, cases born from 2005 to 2010 had a three-fold increased unadjusted odds of elevated exposure compared to controls born in this same time period (4th Quartile OR: 3.53, 95% CI: 1.35, 9.27). Furthermore, the estimates for children with acute myeloid leukemia (AML) were stronger than those with acute lymphoid leukemia, though not statistically significant. CONCLUSIONS: While we did not observe an association between benzene and childhood leukemia overall, our results suggest that acute leukemia is associated with increased benzene exposure among more recent births, and children with AML may have increased benzene exposure at birth. Using the NATA estimates allowed us to assess a specific pollutant at the census tract level, providing an advantage over monitor or point source data. Our study, however, cannot rule out the possibility that benzene may be a marker of other traffic-related exposures and temporal misclassification may explain the lack of an association among earlier births.

Lifestyle factors associated with histologically derived human ovarian non-growing follicle count in reproductive age women.

STUDY QUESTION: Are lifestyle factors (smoking, BMI, alcohol use and oral contraceptive pill use) associated with the human ovarian reserve as determined by the total ovarian non-growing follicle number? SUMMARY ANSWER: Light to moderate alcohol use was significantly associated with greater ovarian non-growing follicle (NGF) count, whereas other lifestyle factors were not significantly related. WHAT IS KNOWN ALREADY: A single previous investigation has suggested that smoking and alcohol use are associated with lower ovarian follicle density. However, this investigation utilized follicle density as the outcome of interest rather than the estimated total ovarian NGF count. STUDY DESIGN, SIZE, DURATION: This cross-sectional investigation included a convenience sample of premenopausal women from two different academic sites, the University of Washington (n = 37, from 1999-2004) and the University of Oklahoma (n = 73, from 2004-2013), undergoing incidental oophorectomy at the time of hysterectomy (total n = 110, age range 21-52 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Prior to undergoing oophorectomy, participants completed detailed questionnaires regarding lifestyle exposures. Following surgery, total ovarian NGF counts were determined with systematic random sampling rules and a validated fractionator/optical dissector technique. Associations between lifestyle factors and log-transformed ovarian follicle counts were determined using multivariable linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: After controlling for age, BMI, oral contraceptive pill (OCP) use, tobacco use and site of collection, cumulative alcohol use (measured in alcoholic drinks per day multiplied by years of drinking) was associated with ovarian NGF count. Women reporting light (>0 to <1 drink-years) and moderate (1-3 drink-years) alcohol use had greater NGF counts (ß = 0.75, P = 0.04, and ß = 1.00, P = 0.03; light and moderate use, respectively) as compared with non-users. Neither heavier alcohol use (>3 drink-years), BMI, OCP use, nor tobacco use were significantly associated with the ovarian NGF count. Similar patterns of association with moderate cumulative alcohol use were observed when evaluating associations with pre-antral follicles and total follicle counts. LIMITATIONS, REASONS FOR CAUTION: All participants in this convenience sample had a benign indication for hysterectomy, and therefore may not be broadly representative of the population without such an indication. Additionally, lifestyle factors were self-reported, and the sample size of the present investigation limits our ability to detect associations of smaller magnitude. WIDER IMPLICATIONS OF THE FINDINGS: While our findings are in disagreement with a single investigation that utilized human follicle density as the outcome of interest, they are consistent with many studies investigating the relationship between lifestyle factors and the age of spontaneous menopause. Furthermore, they suggest a mechanism that does not involve accelerated follicular atresia to explain the association between smoking and an earlier age of menopause. STUDY FUNDING/COMPETING INTERESTS: This investigation was funded by NIA R29-HD37360-04 (N.A.K.) and OCAST HR04-115 (K.R.H.) and by the National Institute of General Medical Sciences, Grant 1 U54GM104938 (J.D.P.). There is no conflict of interest.