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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.

Objective To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. Design Retrospective cohort study. Setting A university-based reproductive endocrinology and infertility clinic. Patient(s) Retrospective review of 1,957 IUI cycles performed on 660 patients between July 2007 and May 2012. Intervention(s) None. Main Outcome Measure(s) The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. Result(s) Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs. 6.8%, respectively, RR = 0.82, 95% CI [0.53–1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% vs. 10.0% (RR = 0.99, 95% CI [0.73–1.35]). Positive serum pregnancy tests after IUI did not differ by regurgitation status (15.0% vs. 15.4%, RR = 0.97, 95% CI [0.75–1.24]). Results were unchanged when adjusted for covariates (age, race and ethnicity, body mass index, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation). Conclusion(s) The presence of regurgitation during the IUI procedure is not related to pregnancy outcome.

STUDY QUESTIONAre intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility?SUMMARY ANSWERPatient 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 KNOWNWe 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, DURATIONThis 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, METHODSAMIGOS 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 CHANCEAfter 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 CAUTIONThis 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 FINDINGSMost 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 NUMBERn/a

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.

Objective The aim of this study was to evaluate the effect of a policy to deliver at 39 weeks for class III obesity. Methods This was a retrospective cohort study of women with class III obesity delivering at ≥ 37 weeks before (May 2012 to April 2014) and after the policy (September 2014 to August 2016). The primary outcome was the cesarean rate. Secondary outcomes included maternal morbidities and a neonatal morbidity composite. Modified Poisson regression was used to adjust for demographic differences between groups. Results The study included a total of 1,210 patients, 580 before the policy and 630 after the policy. Before and after the policy, cesarean rates were similar (41.6% vs. 47.1%; risk ratio [RR]: 1.13 [95% CI: 1.00-1.29]; adjusted RR [aRR]: 1.03 [95% CI: 0.92-1.14]). In adjusted comparisons of women undergoing labor induction, parous women had lower cesarean rates (aRR: 0.62; 95% CI: 0.41-0.94) but nulliparous women had higher cesarean rates (aRR: 1.32; 95% CI: 1.04-1.68) after the policy (P for interaction = 0.01). Rates of chorioamnionitis, endometritis, and cesarean wound infection were not different between groups. Composite neonatal morbidity was not different between pre- and postpolicy groups. Conclusions A policy of delivery at 39 weeks for class III obesity did not affect overall cesarean rate or rates of maternal or neonatal morbidity. Further investigation should evaluate subsets of women who may have a higher cesarean rate with this policy.

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.

INTRODUCTION Congenital anomalies were the leading cause of infant mortality, responsible for 23 and 21% of deaths in Oklahoma and the USA, respectively, in 2016. We aimed to determine the prevalence by race/ethnicity and spatial distribution of congenital anomalies to identify geographic and racial/ethnic disparities, particularly among American Indian/Alaska Natives (AI/AN). METHODS We evaluated the prevalence of anomalies by type and race/ethnicity among 648,074 live births in Oklahoma from 1997 to 2009. Prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. We used Moran's I and Getis-Ord Gi* to evaluate spatial clustering for neural tube defects, critical congenital heart defects (CCHDs), and oral clefts among births whose residence geocoded to the ZIP code or finer level. RESULTS Overall prevalence of anomalies among live births was 3.9%. Non-Hispanic (NH) African American (PPR: 0.87, 95% CI: 0.83, 0.91), Asian/Pacific Islander (PPR: 0.70, 95% CI: 0.63, 0.78), and Hispanic (PPR: 0.87, 95% CI: 0.83, 0.91) children had a lower prevalence of anomalies compared to NH whites. The prevalence in NH AI/AN children was similar to NH whites (PPR: 1.01, 95% CI: 0.97, 1.05). However, differences in specific types of anomalies were observed by race/ethnicity. We observed no spatial autocorrelation for CCHD and oral clefts. Neural tube defects demonstrated spatial autocorrelation (p

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.

Women with obesity are at increased risk of complications during and after labor and delivery, including puerperal infection and cesarean delivery. As labor induction has become increasingly common, it is crucial to find ways to decrease complication rates in this high-risk population.This study aimed to explore the effect of prophylactic antibiotics during labor induction of nulliparous women with obesity on the rates of cesarean delivery and puerperal infection and to estimate the parameters needed to calculate the sample size for a larger, multicenter trial.In this randomized, placebo-controlled pilot trial, nulliparous patients with a body mass index of ≥30 kg/mFrom January 2019 to May 2021, 101 patients were randomized in the class III stratum (1 patient who was randomized ultimately did not undergo labor induction). From February 2020 to May 2021, 38 and 47 patients were randomized to class I and II strata, respectively (to assess the effect of obesity class on the outcomes expected to be influenced by antibiotic prophylaxis). In the antibiotics and placebo groups, the rates of cesarean delivery were 29.0% (95% confidence interval, 19.8-38.3) and 39.8% (95% confidence interval, 29.8-49.7), respectively, and puerperal infection occurred in 8.6% (95% confidence interval, 2.9-14.3) and 9.7% (95% confidence interval, 3.7-15.7), respectively. In the subgroup with class III obesity, in the antibiotics and placebo groups, the rates of cesarean delivery were 33.3% (95% confidence interval, 20.4-47.9) and 46.0% (95% confidence interval, 32.2-59.8), respectively, and puerperal infection occurred in 7.8% (95% confidence interval, 0.5-15.2) and 10.0% (95% confidence interval, 1.7-18.3), respectively. Note that this pilot study was not powered to detect differences of this magnitude but rather to estimate parameters.The administration of prophylactic antibiotics during labor induction of nulliparous patients with obesity resulted in a 27% lower cesarean delivery rate overall and a 28% lower rate in patients with class III obesity. A larger trial is warranted to evaluate these differences.

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.

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 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 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.

Previous studies suggest arsenic exposure may increase the risk of gestational diabetes mellitus (GDM). However, prior assessments of total arsenic concentrations have not distinguished between toxic and nontoxic species. Our study aimed to investigate the relationships between inorganic arsenic exposure, arsenic methylation capacity, and GDM. Sixty-four cases of GDM and 237 controls were analyzed for urinary concentrations of inorganic arsenic species and their metabolites (arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)), and organic forms of arsenic. Inorganic arsenic exposure was defined as the sum of inorganic and methylated arsenic species (iSumAs). Methylation capacity indices were calculated as the percentage of inorganic arsenic species [iAs% = (As3 + As5)/iSumAs, MMA% = MMA/iSumAs, and DMA% = DMA/iSumAs]. Multivariable logistic regression was performed to evaluate the association between inorganic arsenic exposure, methylation capacity indices, and GDM. We did not observe evidence of a positive association between iSumAs and GDM. However, women with GDM had an increased odds of inefficient methylation capacity when comparing the highest and lowest tertiles of iAs% (adjusted odds ratio (aOR) = 1.48, 95% CI 0.58–3.77) and MMA% (aOR = 1.95 (95% CI 0.81–4.70) and a reduced odds of efficient methylation capacity as indicated by DMA% (aOR = 0.62 (95% CI 0.25–1.52), though the confidence intervals included the null value. While the observed associations with arsenic methylation indices were imprecise and warrant cautious interpretation, the direction and magnitude of the relative measures reflected a pattern of lower detoxification of inorganic arsenic exposures among women with GDM.

OBJECTIVE: To study the association of endometrial thickness (EMT) with live birth rates (LBR) in ovarian stimulation with intrauterine insemination (OS-IUI) treatments for unexplained infertility DESIGN: Prospective cohort analysis of the Reproductive Medicine Network’s Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial SETTING: multicenter randomized controlled trial PATIENTS: 868 couples with unexplained infertility (n=2459 cycles) INTERVENTIONS: OS-IUI treatment cycles (n = 2,459) as part of the AMIGOS clinical trial MAIN OUTCOME MEASURES: Live birth rates (LBR); unadjusted and adjusted risk ratios (RR) for live birth by EMT category calculated using generalized estimating equations. RESULTS: The overall mean EMT on day of hCG administration in cycles with a live birth (9.5 mm, 95% CI 9.1–9.8) was significantly greater than in those without (8.9, 8.8–9.1; p=0.004). Compared to the referent EMT group of 9–12 mm, the unadjusted RR for live birth for the EMT groups of ≤5 and 6–8 were 0.48 (95% CI 0.22–1.03) and 0.92 (0.69–1.23), respectively. The test for trend indicated evidence of decreasing LBR with decreasing EMT (p=0.03). After adjustment for ovarian stimulation medication, a linear trend was no longer supported (p=0.41). Stratified analyses revealed no differences in associations by treatment group. CONCLUSIONS: In OS-IUI for unexplained infertility, higher LBR are observed with increasing EMT; however, EMT is not significantly associated with LBR when adjusted for OS treatment type. Appreciable LBR are seen at all EMTs, even those of ≤5 mm, suggesting that OS-IUI cycles should not be canceled for thin endometrium. TRIAL REGISTRATION: clinicaltrials.gov NCT01044862

IntroductionThe nine-valent human papillomavirus (HPV) vaccine could prevent an estimated 92% of the cancers attributable to HPV types targeted by the vaccine. However, uptake of the HPV vaccine among American Indian and Alaska Native (AI/AN) adolescents has been low. AI/ANs also bear a disproportionate burden of cervical and other HPV-associated cancers. Increasing HPV vaccination rates is a national priority, but reviews and national surveys on HPV vaccination factors are lacking for the AI/AN population. The objective of this systematic review is to assess factors associated with HPV vaccination among AI/ANs in the USA.Methods and analysisA systematic review is proposed to synthesise the current literature on HPV vaccination factors in AI/ANs from 1 July 2006 until 30 September 2019. As applicable, controlled vocabulary terms, keywords and special features (eg, limits, explode and focus) will be incorporated into database searches. To maximise the identification of relevant studies, citation indexes and databases that index dissertations, preprints and grey literature are included. Studies will be screened and selected independently in two stages. In stage 1, titles and abstracts will be screened. In stage 2, full-text articles will be screened and selected. A data extraction form and quality assessment tool will be piloted, revised and implemented. If available, measures of frequency and association will be presented. A narrative synthesis of the included studies will also be undertaken and reported.Ethics and disseminationAs our review will use publicly available data and publications, an Institutional Review Board review will not be required. We will disseminate the findings from this review through peer-reviewed publication(s) and conference presentation(s).Potential amendmentsIn the event of amendments to the protocol, we will provide the date, rationale, and description of the change for each amendment.PROSPERO registration numberCRD42020156865.

OBJECTIVE: The goal of this study was to evaluate differences in levator ani hematoma formation within 3 days of delivery between adult women after their first vaginal delivery and adult women who have had multiple vaginal deliveries. METHODS: This was a cross-sectional study at a single institution from 2013 to 2015 using a high-resolution endovaginal ultrasound transducer to identify postvaginal delivery hematoma formation. Logistic regression was used to examine the association between hematoma formation and vaginal parity while considering potential confounders including induction, vaginal operative delivery, vaginal birth after cesarean, fetal weight, fetal head circumference, race and ethnicity, body mass index, age at delivery, gestational age, and length of second-stage labor. RESULTS: Ninety women (46 vaginal-primiparous; 44 vaginal-multiparous) were included in this study. After adjusting for oxytocin use, length of second-stage labor, and body mass index, the odds of pelvic floor hematoma of 1000 mm(3) or greater were 2.93 (95% confidence interval, 0.78–10.91) times greater in women after their first vaginal delivery compared with women with a history of multiple vaginal deliveries. The adjusted odds of pelvic floor hematoma of 1500 mm(3) or greater were 6.02 (95% confidence interval, 1.09–33.24) times greater in vaginal-primiparous compared with vaginal-multiparous women. CONCLUSIONS: Although the prevalence of pelvic floor hematoma was higher in vaginal-primiparous women than vaginal-multiparous women after vaginal delivery, hematomas were present in both groups. Future prospective studies are needed to evaluate the additive effect of multiple vaginal deliveries on the pelvic floor.

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.

We evaluated endometrial pattern (defined as the relative echogenicity of the endometrium on a longitudinal uterine ultrasonic section) as a surrogate for endometrial receptivity in an attempt to evaluate the association between endometrial pattern and pregnancy outcome in women who underwent ART treatment. The primary outcome was live birth and secondary outcomes were clinical intrauterine pregnancy and miscarriage. Potential associations were evaluated using cluster-weighted generalized estimating equations to account for within-couple correlation among repeated ART cycles while adjusting for potentially confounding variables. There were 1034 ART cycles with embryo transfer (778 fresh, 256 frozen) among 695 women (median age: 31.0 (6.0) years). The average number of embryos transferred per cycle was 2.1 embryos. The clinical intrauterine pregnancy rate per transfer was 56.0% for fresh and 54.3% for frozen cycles. The overall live birth rate per embryo transfer was 48.4%. Live birth rates were unchanged when the endometrium was semi-trilinear (RR:0.91 CI:0.74,1.12) or unilinear (RR:1.15 CI:0.89,1.49) in comparison to trilinear endometrium after controlling for potentially confounding variables. Results were similar when analysed separately for fresh and frozen cycles and when evaluating associations with clinical intrauterine pregnancy and miscarriage rates. It appears that endometrial pattern does not significantly affect live birth in ART and our data do not support cancelling an ART cycle if the endometrium is less than trilinear.

Objectives The aim of this study was to determine the prevalence of opioid pain medication use among patients presenting for a new visit to the urogynecology clinic compared with those presenting to general gynecology. Methods We identified all patients who presented for new patient visits to the urogynecology and gynecology clinics between January 1, 2016, and December 31, 2016. Any previous or current opioid use was extracted from the electronic medical record medication list. Statistical analysis was performed using χ and Fisher exact tests for comparisons of categorical variables. Modified Poisson regression models were used to estimate prevalence proportion ratios (PPRs). Results There were 1835 (955 gynecology, 880 urogynecology) patients included. Median age was 47 years (interquartile range, 29 years), and median body mass index was 28.15 kg/m (interquartile range, 9.96 kg/m). Prevalence of opioid use was lowest among women who identified as Asian or other race and highest among black and Native American women; however, when compared by ethnicity, use was lowest among Hispanic women (P = 0.01). Among new urogynecology patients, 14% had self-reported opioid pain medication usage. Opioid use was almost twice as likely in the urogynecology group (PPR, 1.86; 95% confidence interval, 1.4-2.4). When adjusted for confounders, the urogynecology group was 1.3 times as likely to report opioid use (PPR 1.29; 95% confidence interval, 1.0-1.8), with this result approaching statistical significance. Conclusions Opioid use is greater in patients presenting to the urogynecology clinic compared with general gynecology. Urogynecologists need to know this information for planning and optimizing pain management in this population.

ObjectivesAlthough 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.MethodsWe 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.ResultsMedian 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.ConclusionsOur 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.

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.

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. P...

Objective To assess whether type of milk supplementation provided to breastfeeding late preterm infants was associated with hospital length of stay (LOS) or breastfeeding status at discharge. Design Retrospective chart review. Setting Tertiary care teaching hospital in the southern United States. Participants Late preterm infants 35 0/7 to 36 6/7 weeks gestational age (N = 183) admitted to the mother-baby unit between November 1, 2014, and October 31, 2016. Methods The exposure of interest was type of milk supplementation, for example, expressed human milk, pasteurized donor human milk, and formula. Outcomes measured were LOS and breastfeeding status at discharge. Generalized Poisson regression models were used to compare LOS by type of milk supplementation. Modified Poisson regression models were used to estimate risk ratios and 95% confidence intervals for associations with breastfeeding status at discharge. Results The LOS for breastfed infants supplemented with expressed human milk and/or pasteurized donor human milk did not differ significantly from exclusively breastfed infants who received no supplement. Exclusively formula-fed infants had longer LOS of 3.2 days compared with 2.6 days for exclusively breastfed infants (p = .001). Breastfed infants who received any formula supplementation were 16% less likely to continue breastfeeding until day of discharge compared with breastfed infants who received human milk supplementation (risk ratio = .84, 95% confidence interval [.77, .92]). Conclusion The high prevalence of supplementation among breastfeeding late preterm infants underscores the potential effect of type of milk supplementation on LOS and breastfeeding outcomes. Our findings suggest that human milk supplementation discourages transition to formula feeding before hospital discharge without increasing LOS.

Objectives We measured biomarkers of exposure among American Indian (AI) ENDS users, smokers, and dual users. Methods Urine was analyzed for total nicotine equivalents (TNE) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol(NNAL). Expired-air carbon monoxide (CO) was collected. Two analyses were performed. "CO analysis" included smokers and dual users whose CO was ≥ 6 ppm and ENDS users whose CO was < 6 ppm. "NNAL analysis" included smokers and dual users whose NNAL was ≥ 47.3 pg/mg, and ENDS users whose NNAL was < 47.3 pg/mg. Biomarkers were summarized by geometric means (GM) and compared with nonparametric tests. Results In both analyses, TNE was no different across the groups, and NNAL and CO were lower in ENDS users. In the NNAL analysis the GM of NNAL was 261.4, 6.1, and 228.0 pg/mg among smokers, ENDS users, and dual users (p < .001). Also in the NNAL analysis, the GM of CO was 14.7, 2.4, and 16.8 ppm among smokers, ENDS users, and dual users (p < .001). Conclusions ENDS users did not differ in nicotine and had lower exposure to a lung carcinogen and a cardiovascular toxicant than smokers or dual users. Dual users and smokers did not differ in biomarker levels. Results should be used to inform tribal regulations and to educate the AI community on ENDS.

BACKGROUND: No research exists on American Indian pregnancy rates following infertility treatment. Most racial/ethnic fertility research has focused on pregnancy following in vitro fertilization, with only rare studies looking at intrauterine insemination (IUI). The objective of our study was to compare fecundability following IUI by race/ethnicity, with a special focus on American Indians. METHODS: This was a retrospective analysis of subjects undergoing IUI July 2007—May 2012 at a university-based infertility clinic. The primary outcome was positive pregnancy test, with a secondary outcome of ongoing pregnancy/delivery (OP/D). We calculated risk ratios (RR) and 95% confidence intervals (CI) using cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. RESULTS: A total of 663 females (median age 32) undergoing 2007 IUI cycles were included in the analysis. Pregnancy rates overall were 15% per IUI cycle. OP/D rates overall were 10% per IUI cycle. The American Indian patients had significantly lower pregnancy (RR 0.34, 95%CI 0.16–0.72) and OP/D rates (RR 0.33, 95%CI 0.12–0.87) compared to non-Hispanic whites when patient and cycle characteristics were controlled. Pregnancy and OP/D rates for blacks, Asians and Hispanics did not differ from non-Hispanic whites. CONCLUSIONS: Our finding of lower IUI treatment success among American Indian patients is novel, as no published studies of assisted reproductive technology or other fertility treatments have examined this subgroup separately. Further investigation of patient and clinical factors that may mediate racial/ethnic disparities in fertility treatment outcomes is warranted.

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.

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.

Background While many studies have evaluated the association between acute childhood leukemia and environmental factors, knowledge is limited. Ambient air pollution has been classified as a Group 1 carcinogen, but studies have not established whether traffic-related air pollution is associated with leukemia. The goal of our study was to determine if children with acute leukemia had higher odds of exposure to traffic-related air pollution at birth compared to controls. Methods We conducted a case-control study using the Oklahoma Central Cancer Registry to identify cases of acute leukemia in children diagnosed before 20 years of age between 1997 and 2012 (n=307). Controls were selected from birth certificates and matched to cases on week of birth (n=1013). Using a novel satellite-based land-use regression model of nitrogen dioxide (NO 2 ) and estimating road density based on the 2010 US Census, we evaluated the association between traffic-related air pollution and childhood leukemia using conditional logistic regression. Results The odds of exposure to the fourth quartile of NO 2 (11.19–19.89 ppb) were similar in cases compared to controls after adjustment for maternal education (OR: 1.08, 95% CI: 0.75, 1.55). These estimates were stronger among children with acute myeloid leukemia (AML) than acute lymphoid leukemia, with a positive association observed among urban children with AML (4th quartile odds ratio: 5.25, 95% confidence interval: 1.09, 25.26). While we observed no significant association with road density, male cases had an elevated odds of exposure to roads at 500 m from the birth residence compared to controls (OR: 1.39, 95% CI: 0.93, 2.10), which was slightly attenuated at 750 m. Conclusions Although we observed no association overall between NO 2 or road density, this was the first study to observe an elevated odds of exposure to NO 2 among children with AML compared to controls suggesting further exploration of traffic-related air pollution and AML is warranted.

Background Data-linkage studies have reported an association between congenital anomalies and childhood cancer. However, few studies have focused on the differences in the effect of congenital anomalies on cancer as a function of attained age. We aimed to examine associations between anomalies and childhood cancer as a function of attained age among children born in Oklahoma. Methods Data were obtained from the Oklahoma State Department of Health from 1997 to 2009 (n = 591,235). We linked Vital Statistics records for singleton deliveries to the Oklahoma Birth Defects Registry and the Oklahoma Central Cancer Registry using name and birth date. To assess the relation between anomalies and childhood cancer, we used Cox regression analysis allowing for a nonproportional hazards for anomalies as a function of age. Results There were 23,368 (4.0%) children with anomalies and 531 (0.1%) children with cancer. When considering 3-year age intervals, we detected an increased hazard of any childhood cancer in children with anomalies compared with those without anomalies before 1 year of age (hazard ratio, 14.1; 95% confidence interval, 8.3–23.7) and at 3 years of age (hazard ratio, 2.3; 95% confidence interval, 1.6–3.2). The increased hazard declined with increasing time since birth, with the effect diminished by 6 years of age. Conclusion Our results were consistent with previous studies indicating an increased rate of childhood cancer among children with anomalies at younger ages. Furthermore, our study added a methodological refinement of assessing the effect of anomalies as a function of attained age. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc.

In 2016–2017, we conducted and published a systematic review on caffeine safety [1] that set out to determine whether conclusions presented in the heavily cited Health Canada assessment, Nawrot et al. [2], remain supported by more recent data. To that end, we reviewed data from 380 studies published between June 2001 and June 2015, which were identified from an initial batch of over 5,000 articles through a stringent search and evaluation process [1]. In the current paper, we use plain language to summarize our process and findings, with the intent of sharing additional context for broader reach to the general public. We addressed whether caffeine doses previously determined not to be associated with adverse effects by Health Canada (400 mg/day for healthy adults, 300 mg/day for pregnant women, 2. 5 mg/kg body weight/day for adolescents and children, and 10 g/day for acute effects) remain appropriate for five outcome areas (acute toxicity, cardiovascular toxicity, bone & calcium effects, behavior, and development and reproduction) in healthy adults, pregnant women, adolescents, and children. We used a weight-of-evidence approach to draw conclusions for each of the five outcomes, as well as more specific endpoints within those outcomes, which considered study quality, consistency, level of adversity, and magnitude of response. In general, updated evidence confirms the levels of intake put forth by Nawrot et al., as not being associated with any adverse health effects, and our results support a shift in caffeine research from healthy to sensitive populations.

Background Studies comparing serum 25-hydroxyvitamin D concentrations in women with and without polycystic ovary syndrome (PCOS) have produced inconsistent results. Additionally, no previous studies have evaluated associations between vitamin D and specific PCOS phenotypes. Methods This case-control study was conducted among women undergoing intrauterine insemination. Cases (N.=137) were diagnosed with PCOS and then further classified into 3 diagnostic phenotypes based on combinations of the Rotterdam criteria (ovulatory dysfunction+polycystic ovaries [N.=55]; ovulatory dysfunction +androgen excess [N.=15]; and ovulatory dysfunction, +polycystic ovaries, +androgen excess [N.=67]). Controls (N.=103) were ovulatory women without PCOS who were undergoing IUI. Serum total 25-hydroxyvitamin D concentrations were categorized as deficient (≤20 ng/mL), insufficient (21-29 ng/mL), and sufficient (≥30 ng/mL). Prevalence odds ratios (PORs) were calculated using logistic regression. Results A higher proportion (59.9%) of PCOS cases lacked sufficient vitamin D levels compared to controls (47.6%; P value=0.06). The odds of vitamin D deficiency in all PCOS cases were twice that of controls (POR=2.03, 95% CI 0.97-4.26); however, the association was attenuated after adjusting for Body Mass Index (BMI) and race/ethnicity (adjPOR=1.43, 95% CI 0.62, 3.26). When examining PCOS phenotypes exhibiting androgen excess, crude associations were observed for deficient vitamin D levels (unadjPOR=2.93, 95% CI: 1.27, 6.77); however, the association decreased after adjustment for BMI and race/ethnicity (adjPOR=2.03, 95% CI: 0.79, 5.19). Conclusions Vitamin D deficiency occurred more frequently in PCOS cases with androgen excess, but associations were attenuated after adjusting for BMI and race/ethnicity. Combining etiologically distinct PCOS subgroups may obscure associations with lower vitamin D levels and other potential risk factors.

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.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.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.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.