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 the 2016 New Jersey State Inpatient Databases, Healthcare Cost and Utilization Project. Surveillance data were adjusted for misclassification using quantitative bias analysis models to estimate the expected NAS prevalence under a range of PPV/NPV bias scenarios. Results: The 2016 observed NAS prevalence was 0.61%. The misclassification-adjusted prevalence estimates ranged from 0.31–0.91%. 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) is always dependent on the PPV, and sometimes dependent on the NPV. However, NPV is always necessary to understand 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.

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.

Purpose: Our goal was to determine if there are differences by place of residence in visiting a doctor for help getting pregnant in a population-based study. Methods: Using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women's Study, a cohort study of fertility outcomes in reproductive-aged women in Georgia, we fit models to estimate the association between geographic type of residence and seeking help for becoming pregnant. Findings: The prevalence of visiting a doctor for help getting pregnant ranged from 13% to 17% across geographic groups. Women living in suburban counties were most likely to seek medical care for help getting pregnant compared with women living in urbanized counties (adjusted prevalence ratio (aPR) = 1.14, 95% CI: 0.74-1.75); among women who reported infertility this difference was more pronounced (aPR = 1.59, 95% CI: 1.00-2.53). Women living in rural counties were equally likely to seek fertility care compared with women in urbanized counties in the full sample and among women who experienced infertility. Conclusions: Women living in urban and rural counties were least likely to seek infertility care, suggesting that factors including but not limited to physical proximity to providers are influencing utilization of this type of care. Increased communication about reproductive goals and infertility care available to meet these goals by providers who women see for regular care may help address these barriers.

Objective To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study. Design Population-based cohort study. Setting Not applicable. Patient(s) Three hundred ninety-seven female breast cancer survivors aged 22–45 years whose cancer was diagnosed between ages 20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also participated in a clinic visit. Intervention(s) None. Main Outcome Measure(s) Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC] ) after cancer. Result(s) Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI] , 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73). Conclusion(s) Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.

Objective To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer. Design Population-based cohort study. Setting Not applicable. Patient(s) A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis. Intervention(s) None. Main Outcome Measure(s) The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant. Result(s) Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types. Conclusion(s) Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access.

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: 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 (E13G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Results: Total thyroxine (T4) concentrations were positively associated with Pd3G and E13G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T4, respectively) and greater follicular phase maximum E13G (E13G = 41.7 ng/mg Cr for women with high T4 vs E13G = 34.3 and 33.7 ng/mg Cr for women with medium and low T4, 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.

Purpose To investigate potential attenuation of healthy worker biases in populations in which healthy women of reproductive age opt out of the workforce to provide childcare. Methods We used 2013–2015 data from 120,928 U.S. women and men aged 22–44 years participating in the Gallup-Healthways Well-Being Index. We used logistic regression to estimate adjusted prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for associations between health and workforce nonparticipation. Results Women and men reporting poor health were more likely to be out of the workforce than individuals reporting excellent health (POR: 3.7, 95% CI: 3.2–4.2; POR: 6.7, 95% CI: 5.7–7.8, respectively), suggesting potential for healthy worker bias. For women (P <.001) but not men (P =.30), the strength of this association was modified by number of children in the home: POR: 7.3 (95% CI: 5.8–9.1) for women with no children, decreasing to POR: 0.9 (95% CI: 0.6–1.5) for women with four or more children. Conclusions These results are consistent with attenuation of healthy worker biases when healthy women opt out of the workforce to provide childcare. Accordingly, we might expect the magnitude of these biases to vary with the proportion of women with differing numbers of children in the population.

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.

BACKGROUND: In regions where prenatal screening for anencephaly and spina bifida is widespread, many cases of these defects are diagnosed prenatally. The purpose of this study was to estimate the frequency of termination of pregnancy (TOP) following prenatal diagnosis of anencephaly or spina bifida and to investigate factors associated with TOP that might lead to selection bias in epidemiologic studies. METHODS: We included articles indexed in Medline or Embase between 1990 and May 2012 reporting the frequency of TOP following prenatal diagnosis of anencephaly or spina bifida with English-language abstracts, 20 or more prenatally diagnosed cases, and at least half of the study years in 1990 or later. We summarized the frequency of TOP across studies using random-effects metaanalysis and stratified results by fetal and study characteristics. RESULTS: Among the 17 studies identified, 9 included anencephaly and 15 included spina bifida. Nine were from Europe, six were from North America, and one each was from South America and Asia. The overall frequency of TOP following prenatal diagnosis was 83% for anencephaly (range, 59-100%) and 63% for spina bifida (range, 31-97%). There were insufficient data to stratify the results for anencephaly; TOP for spina bifida was more common when the prenatal diagnosis occurred at less than 24 weeks' gestation, with defects of greater severity, and in Europe versus North America. CONCLUSIONS: Because underascertainment of birth defects might be more likely when the pregnancy ends in TOP and TOP is associated with fetal characteristics, selection bias is possible in epidemiologic studies of anencephaly or spina bifida.