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Introduction: Previous studies suggest female smoking increases time-to-pregnancy (TTP), a couple-dependent reproductive outcome, while associations with male smoking are more ambiguous. Furthermore, despite small increases in smokeless tobacco use in the United States, no prior study has evaluated TTP among smokeless tobacco users.Methods: Using population-based sampling in 16 counties in Michigan and Texas, 501 couples discontinuing contraception to become pregnant were followed until positive pregnancy test or 12 months of trying. Participants were interviewed on lifetime and current cigarette, cigar, and chew/snuff (smokeless) use and provided blood samples for quantification of heavy metals and cotinine. Fecundability odds ratios (FORs) and 95% confidence intervals (95% CIs) were estimated, adjusted for demographics/lifestyle. FORs less than 1 reflect longer TTP.Results: Eleven percentage of females and 15% of males smoked cigarettes. Among men, 14% smoked cigars, 9% used snuff, and 2% used chew. Compared with never tobacco users, male (FOR: 0.41, 95% CI: 0.24, 0.68) and female (FOR: 0.53, 95% CI: 0.33, 0.85) smoking were individually associated with longer TTP; males' smoking remained significant (FOR: 0.46, 95% CI: 0.27, 0.79) when modeling partners together. Cadmium levels were higher in smokers than smokeless tobacco and never users; adjusting for cadmium attenuated the cigarette-TTP association, particularly among women. TTP was shorter among smokeless tobacco users relative to smokers (FOR: 2.86, 95% CI: 1.47, 5.57).Conclusions: Compared with never users, smokeless tobacco did not alter TTP in our cohort; however, TTP was shorter compared with smokers. We observed longer TTP in male and female smokers; cadmium may partially contribute.Implications: Both partners' preconception smoking contributed to longer TTP, highlighting the importance of both partners' lifestyles in healthy reproduction and underscores the need for couple-based preconception guidance. The male's contribution is a new finding. Higher cadmium levels may partially contribute to longer TTP in smokers, particularly among females. Though we do not observe longer TTP among a small sample of smokeless tobacco users compared with never tobacco users, we observe shorter TTP compared with smokers. Further work is needed to more thoroughly delineate the relationship between smokeless tobacco use and TTP and possible mechanisms of tobacco use's effects on reproduction. [ABSTRACT FROM AUTHOR]

Infant exposure to per/polyfluoroalkyl compounds is associated with immune disruption. We examined associations between neonatal concentrations of perflurooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and immunoglobulin (Ig) isotype profiles in a prospective cohort of infants. We measured Ig isotypes, including IgA, IgE, IgM and the IgG subclasses IgG 1 , IgG 2 , IgG 3 , and IgG 4, and PFOA and PFOS in newborn dried bloodspots from N = 3175 infants in the Upstate KIDS Study (2008–2010). We examined the association between newborn Ig isotype levels and individual PFOS and PFOA concentrations using mixed effects regression models with a random intercept to account for twins among study participants. We assessed the joint effect PFOA and PFOS with quantile-based g-computation on all singletons and one randomly selected twin (N = 2901), with Ig categorized as above or below median value. Models were adjusted for infant sex, and maternal pre-pregnancy body mass index, race, parity, age and infertility treatment. In adjusted models, PFOA was inversely associated with IgE (coefficient = −0.12 per unit increase in PFOA, 95% CI: −0.065, −0.17), whereas IgG 2 , IgM, and IgA were positively associated with PFOA (coefficient for IgG 2 = 0.22, 95% CI: 0.15, 0.27; coefficient for IgM = 0.11, 95% CI: 0.08, 0.15; and coefficient for IgA = 0.15, 95% CI: 0.07, 0.18). There was no relation between PFOS and Ig isotypes. Analysis of the joint effect of PFOA and PFOS showed an OR of 1.2 (95% CI: 1.04, 1.36) for IgA and OR of 1.12 (95% CI: 1.00, 1.24) for IgG 2 levels above the median for every quartile increase. PFOA levels were significantly associated with elevated IgA, IgM, IgG 2 , and reduced levels of IgE in single-pollutant models. A small but significant joint effect of PFOA and PFOS was observed. Our results suggest that early exposure to PFOA and PFOS may disrupt neonatal immunoglobulin levels. [Display omitted] • Early exposure to PFOA and PFOS may disrupt neonatal immunoglobulin profiles. • PFOA was significantly associated with elevated IgA, IgM, IgG 2 and lower IgE levels. • Analysis yielded a significant joint effect consistent with single-pollutant models. • Effects of PFAS exposure on immunity are measurable even in newborns. [ABSTRACT FROM AUTHOR]

Aim: We examined whether children of mothers with a medical condition diagnosed before or during pregnancy took longer to achieve gross motor milestones up to age 24 months.Method: We obtained information on medical conditions using self-reports, birth certificates, and hospital records in 4909 mothers participating in Upstate KIDS, a population-based birth cohort. Mothers reported on their children's motor milestone achievement at 4, 8, 12, 18, and 24 months of age.Results: After adjustment for covariates (including pre-pregnancy body mass index), children of mothers with gestational diabetes took longer to achieve sitting without support (hazard ratio [HR]=0.84, 95% confidence interval [CI] 0.75-0.93), walking with assistance (HR=0.88, 95% CI 0.77-0.98), and walking alone (HR=0.88, 95% CI 0.77-0.99) than children of females with no gestational diabetes. Similar findings emerged for maternal diabetes. Gestational hypertension was associated with a longer time to achieve walking with assistance. These associations did not change after adjustment for gestational age or birthweight. Severe hypertensive disorders of pregnancy were related to a longer time to achieve milestones, but not after adjustment for perinatal factors.Interpretation: Children exposed to maternal diabetes, gestational or pre-gestational, may take longer to achieve motor milestones than non-exposed children, independent of maternal obesity. [ABSTRACT FROM AUTHOR]

Menstrual cycle length (MCL) has been shown to play an important role in couple fecundity, which is the biologic capacity for reproduction irrespective of pregnancy intentions. However, a comprehensive assessment of its role requires a fecundity model that accounts for male and female attributes and the couple's intercourse pattern relative to the ovulation day. To this end, we employ a Bayesian joint model for MCL and pregnancy. MCLs follow a scale multiplied (accelerated) mixture model with Gaussian and Gumbel components; the pregnancy model includes MCL as a covariate and computes the cycle-specific probability of pregnancy in a menstrual cycle conditional on the pattern of intercourse and no previous fertilization. Day-specific fertilization probability is modeled using natural, cubic splines. We analyze data from the Longitudinal Investigation of Fertility and the Environment Study (the LIFE Study), a couple based prospective pregnancy study, and find a statistically significant quadratic relation between fecundity and menstrual cycle length, after adjustment for intercourse pattern and other attributes, including male semen quality, both partner's age, and active smoking status (determined by baseline cotinine level 100 ng/mL). We compare results to those produced by a more basic model and show the advantages of a more comprehensive approach. [ABSTRACT FROM AUTHOR]

The analysis of fecundity data is challenging and requires consideration of both highly timed and interrelated biologic processes in the context of essential behaviors such as sexual intercourse during the fertile window. Understanding human fecundity is further complicated by presence of a sterile population, i.e. couples unable to achieve pregnancy. Modeling techniques conducted to date have largely relied upon discrete time-to-pregnancy survival or day-specific probability models to estimate the determinants of time-to-pregnancy or acute effects, respectively. We developed a class of semi-parametric grouped transformation cure models that capture day-level variates purported to affect the cycle-level hazards of conception and, possibly, sterility. Our model's performance is assessed using simulation and longitudinal data from one of the few prospective cohort studies with preconception enrollment of women followed for 12 menstrual cycles at risk for pregnancy. [ABSTRACT FROM AUTHOR]

New cervical cancer screening guidelines in the USA and many European countries recommend that women are tested for human papilloma virus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer or cancer risk per year of continued HPV infection. However, both time to onset of precancer or cancer and time to HPV clearance are interval censored, and onset of precancer or cancer strongly informatively censors HPV clearance. We analyse these bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer or cancer by using shared random effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer or cancer. The model was fitted to data on 9553 HPV positive and negative women undergoing cervical cancer screening at Kaiser Permanente Northern California: data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model with those from population-average marginal models of precancer or cancer risk. In particular, after 2 years the marginal population-average precancer or cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models that can predict individual risk may have implications that are different from those of population-average risk models that are currently used for informing medical guideline development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study the relationship between acute air pollution exposure and cardiovascular events during labour/delivery. METHODS: The Consortium on Safe Labor (2002-2008), an observational US cohort with 223502 singleton deliveries provided electronic medical records. Air pollution exposure was estimated by modified Community Multiscale Air Quality models. Cardiovascular events (cardiac failure/arrest, stroke, myocardial infarcts and other events) were recorded in the hospital discharge records for 687 pregnancies (0.3%). Logistic regression with generalised estimating equations estimated the relationship between cardiovascular events and daily air pollutant levels for delivery day and the 7days preceding delivery. RESULTS: Increased odds of cardiovascular events were observed for each IQR increase in exposure to nitric oxides at 5 and 6days prior to delivery (OR=1.17, 99% CI 1.04 to 1.30 and OR=1.15, 1.03 to 1.28, respectively). High exposure to toxic air pollution species such as ethylbenzene (OR=1.50, 1.08 to 2.09), m-xylene (OR=1.54, 1.11 to 2.13), o-xylene (OR=1.51, 1.09 to 2.09), p-xylene (OR=1.43, 1.03 to 1.99) and toluene (OR=1.42, 1.02 to 1.97) at 5days prior to delivery were also associated with cardiovascular events. Decreased odds of events were observed with exposure to ozone. CONCLUSIONS: Air pollution in the days prior to delivery, especially nitrogen oxides and some toxic air pollution species, was associated with increased risk of cardiovascular events during the labour/delivery admission. [ABSTRACT FROM AUTHOR]