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Planning study visits during specific menstrual cycle phases is important if the exposure or outcome is influenced by hormonal variation. However, hormone profiles differ across cycles and across women. The value of using fertility monitors to time clinic visits was evaluated in the BioCycle Study (2005-2007). Women aged 18-44 years (mean, 27.4) with self-reported menstrual cycle lengths of 21-35 days were recruited in Buffalo, New York, for 2 cycles (n = 250). Participants were provided with home fertility monitors that measured urinary estrone-3-glucuronide and luteinizing hormone (LH). The women were instructed to visit the clinic for a blood draw when the monitor indicated an LH surge. The monitor recorded a surge during 76% of the first cycles and 78% of the second cycles. Scheduling visits by using set cycle days or algorithms based on cycle length, such as a midcycle window or a window determined by assuming a fixed luteal phase length, would be simpler. However, even with perfect attendance in a 3-day window, these methods would have performed poorly, capturing the monitor-detected LH surge only 37%-57% of the time. Fertility monitors appear to be useful in timing clinic visits in a compliant population with flexible schedules. [ABSTRACT FROM AUTHOR]

Spontaneous abortion studies that recruit pregnant women are left truncated because an unknown proportion of the source population experiences losses prior to enrollment. Unconditional logistic regression, commonly used in such studies, ignores left truncation, whereas survival analysis can accommodate left truncation and is therefore more appropriate. This study assessed the magnitude of bias introduced by fitting logistic versus Cox models using left-truncated data from a 1998 US pregnancy cohort study (n = 5,104) of trihalomethanes and spontaneous abortion. In addition, the conditions producing bias were explored by using simulated exposure data. The odds ratios and hazard ratios from the actual study differed by 10% or less. However, when the exposed women entered observation earlier on average than those unexposed, the hazard ratio was closer to the null than the odds ratio, whereas the reverse was true when the exposed entered later. The simulation suggests that bias in the odds ratio will exceed 20% when average gestational age at entry for the exposed versus the unexposed differs by 10 days or more, as has been observed regarding some socioeconomic factors, such as education and ethnicity. Cox regression can correct for left truncation and is no more difficult to perform than logistic regression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A physiologic predisposition toward hypertension is theorized to result from the combination of intrauterine growth restriction followed by rapid catch-up growth. The objective of this study was to evaluate the effects of birth weight and weight gain during childhood on the risk for high blood pressure in childhood and to identify discrete periods of catch-up growth that put children with intrauterine growth restriction at increased risk for the development of high blood pressure later in life. METHODS: The US Collaborative Perinatal Project (1959-1974) studied 55,908 pregnancies in an observational cohort at 12 medical centers in the United States and followed the offspring through 7 years of age. All white or black children who were born at term and completed the follow-up without kidney or heart disease were included in this posthoc analysis. z scores were calculated for weight at birth, 4 months, 1 year, 4 years, and 7 years on the basis of study means and SD. Changes in z scores were calculated for each interval. RESULTS: Each 1-kg increase in birth weight increased the odds for high systolic blood pressure by 2.19 and high diastolic blood pressure by 1.82 when race and change in weight z scores were also included in the regression model. An increase in weight z score of 1 SD above the previous weight z score increased the odds for high systolic blood pressure at 7 years by 1.65 (birth to 4 months), 1.79 (4 months to 1 year), 1.71 (1-4 years), and 1.94 (4-7 years) in the full model. White race increased the odds for high systolic blood pressure by 1.51. CONCLUSIONS: In this large biracial US cohort, infants who were small for gestational age were not at increased risk for high blood pressure at 7 years of age. However, children who crossed weight percentiles upward during early childhood did demonstrate an increased risk. [ABSTRACT FROM AUTHOR]

The primary route of mercury exposure for the general population is through consumption of contaminated seafood. There is a biological basis for an adverse effect of mercury exposure on human fertility. The goal of this review was to evaluate the existing literature on the association between mercury and pregnancy, among men and women attempting to conceive with and without assisted reproductive technology (ART). Systematic searches were performed in PubMed, EMBASE, Scopus and Web of Science for papers published up to March 2023 with no early date restriction, only including studies with a biomarker measurement of mercury exposure. We identified 11 studies examining mercury and natural fertility and 12 studies examining mercury and outcomes of assisted reproduction (implantation or clinical pregnancy). The accumulated evidence provides some support for a null association between bodily mercury concentrations and natural fertility among women, however, a large proportion of studies did not report adjusted estimates or were extremely imprecise. The majority of studies of natural fertility were also cross-sectional in nature. There was no evidence for an inverse or null association between mercury and natural fertility among men, or mercury and ART outcomes among men or women. In spite of biological plausibility, the existing evidence includes studies that are imprecise and often conflicting and does not allow us to make definitive conclusions on the associations of mercury exposure with successful pregnancy. Additional, larger studies are warranted, especially among individuals with high concentrations of mercury exposure as these individuals may be underrepresented in the current literature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Disparities in maternal-child health outcomes by race and ethnicity highlight structural differences in the opportunity for optimal health in the United States. Examples of these differences include access to state-level social policies that promote maternal-child health. States vary in their racial and ethnic composition as a result of the complex history of policies and laws related to slavery, Indigenous genocide and relocation, segregation, immigration, and settlement in the United States. States also vary in the social policies they enact. As a result, correlations exist between the demographic makeup of a state's population and the presence or absence of social policies in that state. These correlations become a mechanism by which racial and ethnic disparities in maternal-child health outcomes can operate. In this commentary, we use the example of 3 labor-related policies actively under consideration at state and federal levels (paid parental leave, paid sick leave, and reasonable accommodations during pregnancy) to demonstrate how correlations between state demographics and presence of these state policies could cause or exacerbate racial and ethnic disparities in maternal-child health outcomes. We conclude with a call for researchers to consider how the geographic distribution of racialized populations and state policies could contribute to maternal-child health disparities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer., Design: Population-based cohort study involving detailed interviews regarding reproductive history., Setting: Not applicable., Patients: Female cancer survivors aged 22-45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026)., Exposure: History of cancer vs. no history of cancer., Main Outcome Measure(s): Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity., Results: Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5-11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78-1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46-1.56), using hormones or medications (aHR 0.86, 95% SI 0.46-1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40-5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67-3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost., Conclusion: Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed., Competing Interests: Declaration of Interests L.M.K. has nothing to disclose. L.M.S. reports funding from the National Institute of Health Loan Repayment Program Award Recipient and travel support from the Pacific Coast Reproductive Specialists Scholarship Award Recipient outside the submitted work. A.C.M. reports funding from A Population-Based Study of Fertility in Female Survivors of Young Adult Cancer (Furthering Understanding of Cancer, Health, and Survivorship In Adult Women—FUCHSIA) NIH/NICHD R01 HD066059 PI: Penelope Howards, Ph.D., Epidemiology, Emory University for the submitted work; funding from Reproductive Health of Young Adult Women Who Have Sickle Cell Disease NICHD 1R21HD103030 (PI Penelope Howards) and Sickle Cell Post Transplantation Long Term and Late Effects Registry (STELLAR) NIH/NHLBI OT2HL152762-01 (PI Lakshmanan Krishnamurthi) outside the submitted work. J.B.S. reports funding from A Population-Based Study of Fertility in Female Survivors of Young Adult Cancer (Furthering Understanding of Cancer, Health, and Survivorship In Adult Women— FUCHSIA) NIH/NICHD R01 HD066059 PI: Penelope Howards, Ph.D., Epidemiology, Emory University, for the submitted work; funding from Impact of fertility status on epigenetic indicators of future health risk NICHD 1R21HD110847-01 (PI Anna Knight), DNA methylation differences underlying female reproductive aging 1KO1AG078497-01A1 (PI Anna Knight), Mapping the follicular fluid exposome for environmental determinants of infertility Hercules Pilot Award (PI Anna Knight), Reproductive Health of Young Adult Women Who Have Sickle Cell Disease NICHD 1R21HD103030 (PI Penelope Howards); travel support from AAOGF Donald Schwartz Travel Award for the annual meeting of The American Gynecological and Obstetrical Society (AGOS) and ABOG examiner and subject matter expert; leadership roles Jewish Fertility Foundation, medical advisory council Chair, 2018−2022, Menopause and Ovarian Insufficiency Special Interest Group (MOISIG), American Society for Reproductive Medicine (ASRM) 2019−2023 leadership, Patient Education Committee, American Society for Reproductive Medicine (ASRM) Chair, 2022-present outside the submitted work. P.P.H. reports funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant 1R01HD066059 for the submitted work., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood., Methods: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E 1 3G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH)., Results: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) μg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E 1 3G or FSH levels by category of in-utero PBB exposure., Conclusion: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Objective: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The study's objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD., Methods: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start., Results: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR: <1 to 11.7 months), which is similar to patients with other-ESKD (median 2.6 months, IQR: <1 to 8.8 months)., Conclusions: Among incident patients with ESKD, having a primary diagnosis of LN-ESKD versus other-ESKD is associated with higher rates of early transplant access outcomes. Despite this, patients with LN-ESKD (vs other-ESKD) are less likely to be preemptively referred (i.e., referred prior to ESKD start) for kidney transplant. While providers may no longer be delaying the early steps in the kidney transplantation process among this patient population, there is still room for improvement in the rates of preemptive referral. Access to kidney transplant referral prior to ESKD could result in increased transplant rates and better transplant outcomes for patients with LN-ESKD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: To our knowledge, no studies have explicitly studied the role of hypertensive disorders of pregnancy (HDP) in racial disparities in severe maternal morbidity (SMM)., Methods: Using causal mediation models, we estimated the proportion of the non-Hispanic (NH) Black-White racial disparity in risk of SMM that is explained through the pathway of HDP. We linked 2006-2019 Georgia hospital discharge records with vital statistics birth and fetal death records for NH Black and NH White birthing persons. We used G-estimation of a structural nested mean model to decompose the absolute racial disparity in the incidence of SMM into pathways operating through HDP., Results: NH Black birthing people experienced an excess 56 SMM events (95% confidence interval [CI] = 52, 59) per 10,000 delivery hospitalizations compared with NH White birthing people. If counterfactual disparity measure estimation assumptions hold, the estimated absolute disparity remaining after blocking the causal pathways through HDP was 41 SMM events per 10,000 deliveries (95% CI = 38, 44), suggesting that 26% (95% CI = 12, 40) of the absolute racial disparity would be eliminated if there was no contribution of HDP to SMM risk., Conclusion: Our results are consistent with the hypothesis that intervening to prevent HDP is an important (yet incomplete) pathway for reducing the excess risk among NH Black pregnancies compared with NH White pregnancies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years ( n  = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.

Background: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure-response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial., Methods: The HAPIN trial recruited pregnant women (9-<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure-response subanalysis, we measured 24-h personal exposures to PM 2·5 , carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24-28 weeks and 32-36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata., Findings: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM 2·5 (74·5 μg/m 3 ) was associated with a reduction in birthweight and gestational age Z scores (birthweight: -14·8 g [95% CI -28·7 to -0·8]; gestational age Z scores: -0·03 [-0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 μg/m 3 ; -21·9 g [-37·7 to -6·1]; -0·05 [-0·08 to -0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; -3·1 [-12·1 to 5·8]; -0·003 [-0·023 to 0·017])., Interpretation: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries., Funding: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

First trimester entry into prenatal care is recommended for all women, and especially women with pre-pregnancy conditions. Our objective was to determine whether women with pre-pregnancy conditions were at lower risk of entry after the first trimester (delayed entry) into prenatal care than women without a pre-pregnancy health condition. We used data from 10,890 participants in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Women reported pre-pregnancy conditions and timing of entry into prenatal care during a computer-assisted telephone interview. Multivariable logistic regression analyses were conducted to evaluate whether having a pre-pregnancy condition was associated with delayed entry into prenatal care compared to women without pre-pregnancy conditions. Approximately 13% of women reported delayed entry into prenatal care, and 18% of women reported a pre-pregnancy condition. Delayed entry into prenatal care was not associated with pre-pregnancy cardiometabolic or neurologic conditions. Women with thyroid conditions were less likely to report delayed entry into prenatal care (prevalence odds ratio (OR), 95% confidence interval (CI): 0.55 [0.32, 0.94]), but women with hematologic and respiratory conditions were more likely to report delayed entry into prenatal care (OR: 1.95 [1.00, 3.82] and 1.27 [0.95, 1.72], respectively), compared to those without any chronic conditions. Future research investigating the success of early prenatal care among women with thyroid conditions could identify ways to reduce delayed prenatal care among women with other pre-pregnancy conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Objective: Women with systemic lupus erythematosus (SLE) may experience adverse perinatal outcomes in the years before an SLE diagnosis. Overall, there is limited research on perinatal outcomes among African American women with SLE. We undertook this study to examine the risk of preterm and small-for-gestational age births among African American women with SLE compared to the general population of African American women in a large metropolitan area., Methods: Information about women with SLE was identified from the Georgia Lupus Registry and the Georgians Organized Against Lupus Cohort and was linked with birth certificates by the Georgia Department of Public Health. Births were categorized into occurring more than 3 years before SLE diagnosis, 0-3 years before SLE diagnosis, 0-3 years after SLE diagnosis, or more than 3 years after SLE diagnosis. Comparison birth certificates to African American women in the same geographic area were obtained from the National Center for Health Statistics. We used log-risk models to compare the risk of preterm or small-for-gestational age births among SLE births in each diagnosis timing category to the general population, adjusting for maternal age and education and parity., Results: Births to women with SLE were more likely to occur preterm at 0-3 years before SLE diagnosis (risk ratio [RR] 1.71, 95% confidence interval [95% CI] 1.24-2.35), 0-3 years after SLE diagnosis (RR 2.29, 95% CI 1.70-3.09), and 3 or more years after SLE diagnosis (RR 2.83, 95% CI 2.36-3.38), but not 3 or more years before SLE diagnosis compared to the general population (RR 1.03, 95% CI 0.77-1.38). Similar results were observed for small-for-gestational age births., Conclusion: Our analysis, conducted among African American women, demonstrates an increased risk of adverse perinatal outcomes even before a clinical diagnosis of SLE., (© 2021 American College of Rheumatology.)

Background: Approximately half of all pregnancies in the United States are unintended. However, women who are diagnosed with cancer in their reproductive years may be a unique population. This study examines the prevalence of and identifies factors associated with unplanned pregnancy among cancer survivors. Materials and Methods: Female cancer survivors aged 22-45 years, diagnosed between ages 20-35 years and at least 2 years postdiagnosis, and women with no history of cancer were interviewed about their reproductive histories, including pregnancy intention. Using a random matching process, comparison women were assigned an artificial age at cancer diagnosis equal to that of her cancer survivor match. An adjusted Cox model was fit examining time to unintended pregnancy after cancer for each of 1,000 matches. Cox proportional hazards models were also fit to assess associations between participant characteristics and unplanned pregnancy after cancer among survivors. Results: Cancer survivors ( n  = 1,282) and comparison women ( n  = 1,073) reported a similar likelihood of having an unplanned pregnancy in models adjusted for race, income, history of sexually-transmitted infection, and history of unplanned pregnancy before diagnosis (adjusted hazard ratio [aHR] 1.06, 95% simulation interval 0.85-1.36). After adjusting for confounders, unplanned pregnancy among survivors was associated with age <30 years at diagnosis (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.32-2.44), black race (HR: 1.55, 95% CI: 1.13-2.12; referent: white), receiving fertility counseling (aHR: 1.41, 95% CI: 1.04-1.92), and having at least one child before diagnosis (aHR: 1.44, 95% CI: 1.05-1.97). Conclusion: Cancer survivors and comparison women had similar likelihood of unplanned pregnancy. Rates of unplanned pregnancy after cancer were not higher for cancer survivors compared with comparison women, but 46.4% of survivors with a postcancer pregnancy reported an unplanned pregnancy. Cancer patients may benefit from patient-centered guidelines and counseling before cancer treatment that covers both risks of infertility and risks of unplanned pregnancy.

Background: Validation studies estimating the positive predictive value (PPV) of neonatal abstinence syndrome (NAS) have consistently suggested overreporting in hospital discharge records. However, few studies estimate the negative predictive value (NPV). Even slightly imperfect NPVs have the potential to bias estimated prevalences of rare outcomes like NAS. Given the challenges in estimating NPV, our objective was to evaluate whether the PPV was sufficient to understand the influence of NAS misclassification bias on conclusions of the NAS prevalence in surveillance research., Methods: We used hospital discharge data from the 2016 New Jersey State Inpatient Databases, Healthcare Cost and Utilization Project. We adjusted surveillance data for misclassification using quantitative bias analysis models to estimate the expected NAS prevalence under a range of PPV and NPV bias scenarios., Results: The 2016 observed NAS prevalence was 0.61%. The misclassification-adjusted prevalence estimates ranged from 0.31% to 0.91%. When PPV was assumed to be ≥90%, the misclassification-adjusted prevalence was typically greater than the observed prevalence but the reverse was true for PPV ≤70%. Under PPV 80%, the misclassification-adjusted prevalence was less than the observed prevalence for NPV >99.9% but flipped for NPV <99.9%., Conclusions: When we varied the NPV below 100%, our results suggested that the direction of bias (over or underestimation) was dependent on the PPV, and sometimes dependent on the NPV. However, NPV was important for understanding the magnitude of bias. This study serves as an example of how quantitative bias analysis methods can be applied in NAS surveillance to supplement existing validation data when NPV estimates are unavailable., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Food consumption, particularly of animal-based products, is considered the most important contributor to persistent endocrine disrupting chemical (EDC) exposure. This study aims to describe the association between maternal diet during pregnancy and exposure to persistent EDCs using dietary pattern analysis. This study is based on subsamples of the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=422) and the Norwegian Mother, Father, and Child Cohort Study (MoBa) (N=276) which uses data from the Medical Birth Registry of Norway (MBRN). Women in both studies completed food frequency questionnaires (FFQs) during pregnancy, from which consumption data were categorized into 38 aggregated food groups. Maternal blood samples were collected during pregnancy and concentrations of perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) in serum/plasma were measured. Dietary patterns were identified using reduced rank regression, with blood EDC concentrations as response variables. Within ALSPAC, all patterns (PFAS, PCB, and OCP) were characterized by high consumption of meat, poultry, white fish, and biscuits. In MoBa, high consumption of sausages and burgers (representing processed meats), pasta, and chocolate bars characterized PCB and OCP dietary patterns, while high consumption of cheese characterized the PFAS pattern. Across both cohorts, PFAS patterns were characterized by high consumption of cheese, PCB patterns by high consumption of rice, and OCP patterns by poultry. Dietary patterns explained between 8 and 20% of the variation in serum EDC concentrations, with explained variance being the highest for PCBs in both cohorts. In conclusion, dietary patterns high in animal-based products appear to be associated with persistent EDC concentrations among pregnant women. Diet explains more variation in PCB concentrations than for other persistent EDC classes.

Background: Endocrine disrupting chemical (EDC) exposure is ubiquitous. EDC exposure during critical windows of development may interfere with the body's endocrine system, affecting growth. Previous human studies have examined one EDC at a time in relation to infant growth. By studying mixtures, the human experience can be better approximated., Aims: We investigated the association of prenatal exposure to persistent EDCs (per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with postnatal body size among female offspring., Subjects: We used a sub-sample of the Avon Longitudinal Study of Parents and Children (N = 425), based in the United Kingdom., Study Design: We quantified 52 EDCs in maternal serum collected during pregnancy. We used Bayesian kernel machine regression with a random intercept to examine the association of prenatal concentrations of EDC mixtures with longitudinal postnatal body size measures for each EDC class separately (PFAS, PCBs, and OCPs) and for all three classes combined., Outcome Measures: Weight and height measures at 0, 2, 9, and 19 months were obtained by health professionals as part of routine child health surveillance., Results: The mixture representing all three classes combined (31 chemicals) (n = 301) was inversely associated with postnatal body size. Holding all EDCs in the 31-chemical mixture at the 75th percentile compared to the 50th percentile was associated with 0.15 lower weight-for-age z-score (95% credible interval -0.26, -0.03). Weak inverse associations were also seen for height-for-age and body mass index-for-age scores., Conclusions: These results suggest that prenatal exposure to mixtures of persistent EDCs may affect postnatal body size., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors (perfluoroalkyl and polyfluoroalkyl substances [PFAS], polychlorinated biphenyls [PCBs], and organochlorine pesticides) with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991-1992., Methods: We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15-week gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout Weighted Quantile Sum (WQS) regression and Bayesian kernel machine regression to examine mixtures in 313 mothers., Results: Using WQS regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (β = -55 g, 95% confidence interval [CI] = -89, -22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length., Conclusions: These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body's endocrine system, which can affect growth and developmental outcomes such as puberty. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. We investigated the association of prenatal exposure to persistent EDCs (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with early menarche among female offspring in a nested case-control study within the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the United Kingdom in 1991-1992. Concentrations of 52 EDCs were quantified in maternal serum samples collected during pregnancy. Daughter's age at menarche was ascertained through mailed questionnaires sent annually. We used repeated holdout weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to examine the association between prenatal exposure to multiple EDCs and early menarche (<11.5 (n = 218) vs. ≥11.5 years (n = 230)) for each chemical class separately (PFAS, PCBs, and OCPs) and for all three classes combined. Models adjusted for maternal age at menarche, maternal education, parity, pre-pregnancy body mass index, maternal age, prenatal smoking, and gestational week at sample collection. Mixture models showed null associations between prenatal exposure to EDC mixtures and early menarche. Using WQS regression, the odds ratio for early menarche for a one-decile increase in chemical concentrations for all three classes combined was 0.89 (95% CI: 0.76, 1.05); using BKMR, the odds ratio when all exposures were at the 60th percentile compared to the median was 0.98 (95% CI: 0.91, 1.05). Results suggest the overall effect of prenatal exposure to persistent EDC mixtures is not associated with early menarche., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Epidemiologists have consistently observed associations between prepregnancy obesity and spina bifida in offspring. Most studies, however, used self-reported body mass index (potential for exposure misclassification) and incompletely ascertained cases of spina bifida among terminations of pregnancy (potential for selection bias). We conducted a quantitative bias analysis to explore the potential effects of these biases on study results., Methods: We included 808 mothers of fetuses or infants with spina bifida (case mothers) and 7,685 mothers of infants without birth defects (control mothers) from a population-based case-control study, the National Birth Defects Prevention Study (1997-2011). First, we performed a conventional epidemiologic analysis, adjusting for potential confounders using logistic regression. Then, we used 5,000 iterations of probabilistic bias analysis to adjust for the combination of confounding, exposure misclassification, and selection bias., Results: In the conventional confounding-adjusted analysis, prepregnancy obesity was associated with spina bifida (odds ratio 1.4, 95% confidence interval: 1.2, 1.7). In the probabilistic bias analysis, we tested nine different models for the combined effects of confounding, exposure misclassification, and selection bias. Results were consistent with a weak to moderate association between prepregnancy obesity and spina bifida, with the median odds ratios across the nine models ranging from 1.1 to 1.4., Conclusions: Given our assumptions about the occurrence of bias in the study, our results suggest that exposure misclassification, selection bias, and confounding do not completely explain the association between prepregnancy obesity and spina bifida., (© 2021 Wiley Periodicals LLC.)

Background: Population-based cancer registries provide a resource to recruit young adult cancer survivors who may not be easily identified otherwise., Methods: We compared demographic and cancer-related characteristics of participants in a cohort of female young adult cancer survivors to those of eligible survivors in the Georgia Cancer Registry, a population-based registry in the United States. We examined associations between survivor characteristics and nonparticipation using logistic regression and associations between survivor characteristics and different types of nonparticipation (refusal, unable to contact, or unresolved vs. interviewed) using polytomous regression., Results: The Georgia Cancer Registry was able to contact 60% of eligible women (3,061/5,137). Of those, 78% agreed to study contact ( n = 2,378), and of those, 56% were interviewed ( n = 1,342). Participation was similar across age at contact and at diagnosis but varied across cancer type from 17% for cervical cancer to 32% for breast cancer. White women were slightly more likely to be interviewed (28%) than African American women (23%), which was mostly attributable to greater difficulty in contacting African American women (odds ratio 1.7, 95% confidence interval: 1.5-2.1)., Conclusions: The greatest challenge to recruiting women was contacting them, which differed across some but not all demographic and cancer-related characteristics. When successfully contacted, most survivors agreed to participate., Impact: Population-based cancer registries can serve as an invaluable resource to recruit representative samples of young adult cancer survivors, who are otherwise difficult to identify., (©2021 American Association for Cancer Research.)

Objective: Women with SLE may experience ovarian insufficiency or dysfunction due to treatment or disease effects. Anti-Müllerian hormone (AMH), a marker of ovarian reserve, has been examined in small populations of women with SLE with conflicting results. To date, these studies have included very few African-American women, the racial/ethnic group at greatest risk of SLE., Methods: We enrolled African-American women aged 22-40 years diagnosed with SLE after age 17 from the Atlanta Metropolitan area. Women without SLE from the same area were recruited from a marketing list for comparison. AMH was measured in serum using the Ansh Labs assay (Webster, Texas, USA). We considered AMH levels <1.0 ng/mL and AMH <25th percentile of comparison women as separate dichotomous outcomes. Log-binomial regression models estimating prevalence ratios were adjusted for age, body mass index and hormonal contraception use in the previous year., Results: Our sample included 83 comparison women without SLE, 68 women with SLE and no history of cyclophosphamide (SLE/CYC-) and 11 women with SLE and a history of cyclophosphamide treatment (SLE/CYC+). SLE/CYC+ women had a greater prevalence of AMH <1.0 ng/mL compared with women without SLE (prevalence ratio (PR): 2.90, 95% CI: 1.29 to 6.51). SLE/CYC- women were also slightly more likely to have AMH <1.0 ng/mL (PR: 1.62, 95% CI: 0.93 to 2.82) than comparison women. Results were similar when considering AMH <25th percentile by age of comparison women., Conclusions: Treatment with CYC is associated with low AMH in African-American women with SLE. SLE itself may also be associated with reduced AMH, but to a lesser extent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: Some treatments for systemic lupus erythematosus (SLE) can cause infertility, but the effect of SLE itself on fertility, particularly in African American women, is less clear. We undertook this study to examine infertility experiences in African American women with SLE compared to healthy women., Methods: We enrolled women ages 22-40 years living in the Atlanta metropolitan area who were diagnosed with SLE after age 17 years. Women who had ever been treated with cyclophosphamide or who had a hysterectomy were excluded. African American women ages 22-40 years who were from the same area and recruited from a marketing list were used for comparison. Women were interviewed about their reproductive histories and goals. Periods of infertility were identified as times when women had regular, unprotected sex for ≥12 months without conceiving after 20 years of age. We separately considered any period of infertility and periods of infertility when attempting pregnancy. We used Cox proportional hazards regression to examine the association between SLE and time to infertility. Models were adjusted for age, nulliparity, and smoking. An age-matched analysis was also conducted to examine periods of infertility occurring after SLE diagnosis., Results: Our sample included 75 women with SLE and 154 women without SLE. SLE was associated with any infertility (adjusted hazard ratio [HR adj ] 2.08 [95% confidence interval (95% CI) 1.38-3.15]), but less so with infertility when attempting pregnancy (HR adj 1.30 [95% CI 0.62-2.71]). The matched analysis generated similar point estimates., Conclusion: Women with SLE may be more likely to experience episodes of infertility, but this may not translate to an inability to meet reproductive goals., (© 2019, American College of Rheumatology.)

Background In women with congenital heart defects (CHD), changes in blood volume, heart rate, respiration, and edema during pregnancy may lead to increased risk of adverse outcomes and conditions. The American Heart Association recommends providers of pregnant women with CHD assess cardiac health and discuss risks and benefits of cardiac-related medications. We described receipt of American Heart Association-recommended cardiac evaluations, filled potentially teratogenic or fetotoxic (Food and Drug Administration pregnancy category D/X) cardiac-related prescriptions, and adverse conditions among pregnant women with CHD compared with those without CHD. Methods and Results Using 2007 to 2014 US healthcare claims data, we ascertained a retrospective cohort of women with and without CHD aged 15 to 44 years with private insurance covering prescriptions during pregnancy. CHD was defined as ≥1 inpatient code or ≥2 outpatient CHD diagnosis codes >30 days apart documented outside of pregnancy and categorized as severe or nonsevere. Log-linear regression, accounting for multiple pregnancies per woman, generated adjusted prevalence ratios (aPRs) for associations between the presence/severity of CHD and stillbirth, preterm birth, and adverse conditions from the last menstrual period to 90 days postpartum. We identified 2056 women with CHD (2334 pregnancies) and 1 374 982 women without (1 524 077 pregnancies). During the last menstrual period to 90 days postpartum, 56% of women with CHD had comprehensive echocardiograms and, during pregnancy, 4% filled potentially teratogenic or fetotoxic cardiac-related prescriptions. Women with CHD, compared with those without, experienced more adverse conditions overall (aPR, 1.9 [95% CI, 1.7-2.1]) and, specifically, obstetric (aPR, 1.3 [95% CI, 1.2-1.4]) and cardiac conditions (aPR, 10.2 [95% CI, 9.1-11.4]), stillbirth (aPR, 1.6 [95% CI, 1.1-2.4]), and preterm delivery (aPR, 1.6 [95% CI, 1.4-1.8]). More women with severe CHD, compared with nonsevere, experienced adverse conditions overall (aPR, 1.5 [95% CI, 1.2-1.9]). Conclusions Women with CHD have elevated prevalence of adverse cardiac and obstetric conditions during pregnancy; 4 in 100 used potentially teratogenic or fetotoxic medications, and only half received an American Heart Association-recommended comprehensive echocardiogram.

Context: Menstrual cycle function is determined by a complex endocrine axis that controls the ovaries and endometrium. While the late luteal phase is characterized by declining progesterone and estrogen, how these hormonal profiles relate to menstrual bleeding patterns is not well understood., Objective: Characterize associations between luteal phase hormonal profiles and subsequent menstrual bleeding patterns, specifically spotting before bleeding., Design, Setting, and Participants: We examined creatinine-adjusted urinary estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) levels in relation to spotting in 116 premenopausal women (ages 20-47) who kept daily menstrual diaries and collected first morning urine samples for ≥ 2 consecutive cycles or 1 luteal-follicular transition (n = 283 transitions). We used linear mixed models to estimate associations between luteal phase hormone levels and spotting before bleeding., Main Outcome Measure(s) and Results: Transitions with ≥ 1 days of spotting before menstrual bleeding (n = 118) had greater luteal phase Pd3G levels vs nonspotting transitions (n = 165). Differences in Pd3G between spotting and nonspotting transitions were largest at menses onset (34.8%, 95% confidence interval, 18.9%, 52.7%). Pd3G levels for spotting transitions dropped to similar levels as nonspotting transitions an average of 1 day later, which aligned with the first day of bleeding for transitions with contiguous spotting. Spotting transitions were preceded by slower rates of Pd3G decline than nonspotting transitions, whereas E13G declines were similar., Conclusions: Self-reported bleeding patterns may provide insight into luteal phase Pd3G levels. First bleed appears to be the best choice for defining the end of the luteal phase and achieving hormonal consistency across transitions., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our objective was to examine associations between night shift work and serum anti-Müllerian hormone (AMH) levels. We analyzed 1,537 blood samples from premenopausal female nurses in the Nurses' Health Study II, assayed for AMH. Rotating or permanent night shifts worked in the two weeks before blood collection and years of rotating night shift work were obtained via questionnaire. We found no associations between recent night shifts or rotating night shift work and AMH. The median difference in AMH was 0.3 (95% CI: -0.4, 0.8) ng/mL for ≥5 versus 0 recent night shifts and -0.1 (95% CI: -0.4, 0.3) ng/mL for ≥6 versus 0 years of rotating night shift work. Although we found no associations between night shift work and AMH, this does not preclude associations between night shift work and fertility operating through other mechanisms.

Background: There is limited information on potentially modifiable risk factors for stillbirth, such as gestational weight gain (GWG). Our purpose was to explore the association between GWG and stillbirth using the GWG z-score., Methods: We analyzed 479 stillbirths and 1601 live births from the Stillbirth Collaborative Research Network case-control study. Women with triplets or monochorionic twins were excluded from analysis. We evaluated the association between GWG z-score (modeled as a restricted cubic spline with knots at the 5th, 50th, and 95th percentiles) and stillbirth using multivariable logistic regression with generalized estimating equations, adjusting for pre - pregnancy body mass index (BMI) and other confounders. In addition, we conducted analyses stratified by pre - pregnancy BMI category (normal weight, overweight, obese)., Results: Mean GWG was 18.95 (SD 17.6) lb. among mothers of stillbirths and 30.89 (SD 13.3) lb. among mothers of live births; mean GWG z-score was - 0.39 (SD 1.5) among mothers of cases and - 0.17 (SD 0.9) among control mothers. In adjusted analyses, the odds of stillbirth were elevated for women with very low GWG z-scores (e.g., adjusted odds ratio (aOR) and 95% Confidence Interval (CI) for z-score - 1.5 SD versus 0 SD: 1.52 (1.30, 1.78); aOR (95% CI) for z-score - 2.5 SD versus 0 SD: 2.36 (1.74, 3.20)). Results differed slightly by pre - pregnancy BMI. The odds of stillbirth were slightly elevated among women with overweight BMI and GWG z-scores ≥1 SD (e.g., aOR (95% CI) for z-score of 1.5 SD versus 0 SD: 1.84 (0.97, 3.50))., Conclusions: GWG z-scores below - 1.5 SD are associated with increased odds of stillbirth.

Background: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973-1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function., Methods: In 2004-2006, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine samples for up to 6 months. We assayed the urine samples for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35-42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973-1974 (n = 70)., Results: We observed that high (>3.0 parts per billion [ppb]) and medium (>1.0-3.0 ppb) PBB exposure were associated with lower E13G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure., Conclusion: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

Much of the literature on the healthy worker effect focuses on studies of chronic disease and mortality; however, when studying pregnancy outcomes, these effects might differ because of the short, defined risk periods of most pregnancy outcomes. Three pregnancy-specific healthy worker effects have also been described, but the structure of these effects has not yet been investigated when occupational exposure, and not employment status, is the exposure of interest. We used directed acyclic graphs to examine healthy worker effects in studies of occupational exposures and pregnancy outcomes: the healthy hire effect, the healthy worker survivor effect, the desperation/privilege effect (differential workforce reentry after pregnancy), the reproductively unhealthy worker effect (women with live births leave the workforce, while women with nonlive births do not), and the insecure pregnancy effect (women with adverse pregnancy outcomes reduce their exposures in subsequent pregnancies). Given our assumptions, we conclude that the healthy hire effect, the desperation/privilege effect, the reproductively unhealthy worker effect, and the insecure pregnancy effect result from confounding that can be addressed if data on measured confounders, such as employment status, are available. The presence of the healthy worker survivor effect, however, varies by study design. Different types of healthy worker effects can be present in studies of occupational exposure and pregnancy outcomes, and many of them are easily addressed analytically., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.)

Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women's decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June-July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women's decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36-45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43-60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20-4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.

Background: The objective of this retrospective cohort study was to determine whether women who conceive soon after treatment for cancer have higher risks of adverse pregnancy outcomes., Methods: Vital records data were linked to cancer registry diagnosis and treatment information in 3 US states. Women who conceived their first pregnancy after diagnosis between ages 20 and 45 years with any invasive cancer or ductal carcinoma in situ were eligible. Log-binomial models were used to compare risks in cancer survivors who conceived in each interval to the risks in matched comparison births to women without cancer., Results: Women who conceived ≤1 year after starting chemotherapy for any cancer had higher risks of preterm birth than comparison women (chemotherapy alone: relative risk [RR], 1.9; 95% confidence interval [CI], 1.3-2.7; chemotherapy with radiation: RR, 2.4; 95% CI, 1.6-3.6); women who conceived ≥1 year after starting chemotherapy without radiation or ≥2 years after chemotherapy with radiation did not. In analyses imputing the treatment end date for breast cancer survivors, those who conceived ≥1 year after finishing chemotherapy with or without radiation had no higher risks than women without cancer. The risk of preterm birth in cervical cancer survivors largely persisted but was somewhat lower in pregnancies conceived after the first year (for pregnancies conceived ≤1 year after diagnosis: RR, 3.5; 95% CI, 2.2-5.4; for pregnancies conceived >1 year after diagnosis: RR, 2.4; 95% CI, 1.6-3.5)., Conclusions: In women who received chemotherapy, the higher risk of preterm birth was limited to those survivors who had short intervals between treatment and conception.Cancer 2018;124:000-000., (© 2018 American Cancer Society.)

Purpose: Exposure misclassification, selection bias, and confounding are important biases in epidemiologic studies, yet only confounding is routinely addressed quantitatively. We describe how to combine two previously described methods and adjust for multiple biases using logistic regression., Methods: Weights were created from selection probabilities and predictive values for exposure classification and applied to multivariable logistic regression models in a case-control study of prepregnancy obesity (body mass index ≥30 vs. <30 kg/m 2 ) and cleft lip with or without cleft palate (CL/P) using data from the National Birth Defects Prevention Study (2523 cases, 10,605 controls)., Results: Adjusting for confounding by race/ethnicity, prepregnancy obesity, and CL/P were weakly associated (odds ratio [OR]: 1.10; 95% confidence interval: 0.98, 1.23). After weighting the data to account for exposure misclassification, missing exposure data, selection bias, and confounding, multiple bias-adjusted ORs ranged from 0.94 to 1.03 in nonprobabilistic bias analyses and median multiple bias-adjusted ORs ranged from 0.93 to 1.02 in probabilistic analyses., Conclusions: This approach, adjusting for multiple biases using a logistic regression model, suggested that the observed association between obesity and CL/P could be due to the presence of bias., (Published by Elsevier Inc.)

Background: Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes., Methods: Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E 1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr)., Results: Total thyroxine (T 4 ) concentrations were positively associated with Pd3G and E 1 3G. Women with higher (vs lower) T 4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T 4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T 4 , respectively) and greater follicular phase maximum E 1 3G (E 1 3G = 41.7 ng/mg Cr for women with high T 4 vs E 1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T 4 , respectively)., Conclusions: Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease., (© 2018 John Wiley & Sons Ltd.)

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To compare markers of fertility and ovarian reserve between cancer survivors and cancer-free women with and without polycystic ovary syndrome (PCOS)., Design: Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study-a population-based cohort study., Setting: Not applicable., Patient(s): Female cancer survivors (n = 1,090) aged 22-45 years, diagnosed between ages 20 and 35 years, and at least 2 years after diagnosis; 369 participated in a clinic visit. Three hundred seventy-four reproductive-aged women without cancer also completed a clinic visit., Intervention(s): None., Main Outcome Measure(s): Infertility, time to first pregnancy after cancer diagnosis, and measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC])., Results: Seventy-eight cancer survivors (7.2%) reported a PCOS diagnosis, with 41 receiving gonadotoxic treatment. Survivors with PCOS exposed to gonadotoxic treatment (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.2-4.5) and unexposed (OR 3.4, 95% CI 1.7-6.9) were more likely to report infertility than unexposed survivors without PCOS and were more likely to have fewer children than desired (exposed: OR 2.1, 95% CI 1.0-4.2; unexposed: OR 3.0, 95% CI 1.4-6.8). After adjusting for age, comparison women with PCOS had the highest markers of ovarian reserve (AMH: 2.43 ng/mL, 95% CI 1.22-4.82 ng/mL; AFC: 20.7, 95% CI 15.3-27.8), and cancer survivors without PCOS treated with gonadotoxic agents had the lowest levels (AMH: 0.19 ng/mL, 95% CI 0.14-0.26 ng/mL; AFC: 7.4, 95% CI 6.4-8.5)., Conclusion(s): Despite having higher AMH and AFC on average after cancer treatment, cancer survivors with PCOS were less likely to meet their reproductive goals compared with survivors without PCOS., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the difference in tubal ligation use between rural and urban counties in the state of Georgia, USA., Methods: The study population included 2,160 women aged 22-45. All participants completed a detailed interview on their reproductive histories. County of residence was categorized using the National Center for Health Statistics Urban-Rural Classification Scheme. We estimated the association between urbanization of county of residence and tubal ligation using Cox regression. Among women with a tubal ligation, we examined factors associated with prior contraception use and the desire for more children., Findings: After adjustment for covariates, women residing in rural counties had twice the incidence rate of tubal ligation compared with women in large metropolitan counties (adjusted hazard ratio [aHR] = 2.0, 95% CI = 1.4-2.9) and were on average 3 years younger at the time of the procedure. No differences were observed between small metropolitan and large metropolitan counties (aHR = 1.1, CI = 0.9-1.5). Our data suggest that women from large metropolitan counties are slightly more likely than women from rural counties to use hormonal contraception or long-acting reversible contraception prior to tubal ligation and to desire more children after tubal ligation., Conclusions: Women from rural counties are more likely to undergo a tubal ligation than their urban counterparts. Our results suggest that circumstances regarding opting for tubal ligation may differ between urban and rural areas, and recommendations of alternative contraceptive options may need to be tailored differently for rural areas., (© 2017 National Rural Health Association.)

In a 1989 paper, Marchbanks et al. (Am J Epidemiol. 1989;130(2):259-267) noted inconsistent definitions of infertility across research and clinical practice and examined differences in prevalence estimates across definitions. Since their study, there have been substantial changes in society, technology, and clinical practice related to female reproductive health. In response, we revisited the original paper using data from a recent study among reproductive-aged women. Internal comparisons across various definitions of infertility were made by assessing how many and which women were classified as infertile, their age at infertility, and the probability of spontaneous pregnancy after infertility. Results were also compared with Marchbanks et al. Black women were more likely to be classified as infertile than white women based on the definition "12 months of unprotected intercourse" (40.1% vs. 33.7%) but less likely by "12 months of attempting pregnancy" (14.3% vs. 21.8%) and "visiting a doctor for help getting pregnant" (8.4% vs. 19.7%). After unprotected intercourse for 12 months, 36.1% of women who were attempting pregnancy spontaneously conceived by 6 months compared with 13.5% of women who were not attempting pregnancy. While our results for most infertility definitions were similar to those of Marchbanks et al., prevalence estimates continued to differ across demographic groups by definition., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate whether elective induction of labor between 39 through 41 weeks of gestation, as compared with expectant management, is associated with reduced cesarean delivery and other adverse outcomes among obese women and their offspring., Methods: We conducted a retrospective cohort study using the 2007-2011 California Linked Patient Discharge Data-Birth Cohort File of 165,975 singleton, cephalic, nonanomalous deliveries to obese women. For each gestational week (39-41), we used multivariable logistic regression models, stratified by parity, to assess whether elective induction of labor or expectant management was associated with lower odds of cesarean delivery and other adverse outcomes., Results: At 39 and 40 weeks of gestation, cesarean delivery was less common in obese nulliparous women who were electively induced compared with those who were expectantly managed (at 39 weeks of gestation, frequencies were 35.9% vs 41.0%, respectively [P<.05]; adjusted odds ratio [OR] 0.82, 95% CI 0.77-0.88). Severe maternal morbidity was less frequent among electively induced obese nulliparous patients (at 39 weeks of gestation, 5.6% vs 7.6% [P<.05]; adjusted OR 0.75, 95% CI 0.65-0.87). Neonatal intensive care unit admission was less common among electively induced obese nulliparous women (at 39 weeks of gestation, 7.9% vs 10.1% [P<.05]; adjusted OR 0.79, 95% CI 0.70-0.89). Patterns were similar among obese parous women at 39 weeks of gestation (crude frequencies and adjusted ORs [95% CIs] were as follows: for cesarean delivery, 7.0% vs 8.7% [P<.05] and 0.79 [0.73-0.86]; for severe maternal morbidity, 3.3% vs 4.0% [P<.05] and 0.83 [0.74-0.94]; for neonatal intensive care unit admission: 5.3% vs 7.4% [P<.05] and 0.75 [0.68-0.82]). Similarly, elective induction at 40 weeks of gestation was associated with reduced odds of cesarean delivery, maternal morbidity, and neonatal intensive care unit admission among both obese nulliparous and parous patients., Conclusion: Elective labor induction after 39 weeks of gestation was associated with reduced maternal and neonatal morbidity among obese women. Further prospective investigation is necessary.

It is unclear whether cancer and its treatments increase the risk of adverse pregnancy outcomes. Our aim was to examine whether cancer survivors have higher risks of poor outcomes in pregnancies conceived after diagnosis than women without cancer, and whether these risks differ by cancer type and race. Diagnoses from cancer registries were linked to pregnancy outcomes from birth certificates in three U.S. states. Analyses were limited to the first, live singleton birth conceived after diagnosis. Births to women without a previous cancer diagnosis in the registry were matched to cancer survivors on age at delivery, parity, race/ethnicity and education. Log-binomial regression was used to estimate risk ratios. Cervical cancer survivors had higher risks of preterm birth (Risk ratio = 2.8, 95% Confidence interval: 2.1, 3.7), as did survivors of invasive breast cancer (RR = 1.3, 95% CI: 1.1, 1.7) and leukemia (RR = 2.1, 95% CI: 1.3, 3.5). We observed a higher risk of small for gestational age (SGA) infants (<10% of weight for age based on a national distribution) in survivors of brain cancer (RR = 1.7, 95% CI: 1.1, 2.8) and extranodal non-Hodgkin lymphoma (RR = 2.3, 95% CI: 1.5, 3.6). We did not see an increased risk of infants born preterm, low birth weight, or SGA in pregnancies conceived after ductal carcinoma in situ, thyroid cancer, melanoma, or Hodgkin lymphoma. While our results are reassuring for survivors of many cancers, some will need closer monitoring during pregnancy., (© 2017 UICC.)

Background: In 1973-1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes., Objectives: We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults., Methods: Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004-2006 study and 683 women and men with follow-up during 2012-2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease., Results: Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models., Conclusions: We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302.