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Background: Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results. Methods: Vital status of 49,853 individuals born between 1959 and 1966 to participants in the Collaborative Perinatal Project cohort was determined by a probabilistic linkage to the National Death Index, covering all US deaths occurring from 1979 through 2016. Cox proportional hazard models were used to examine associations of general, verbal, and non‐verbal intelligence at ages 4 and 7, and academic skills at age 7 with suicide death coded according to ICD‐9/10 criteria, while accounting for sociodemographic and pregnancy factors previously associated with suicide in this sample. Results: By the end of 2016, 288 cohort members had died by suicide. Cognitive performance at 7 years on tests with verbal components was associated with suicide risk (average vs. high verbal intelligence, HR = 1.97, 95% CI 1.05–3.71; low vs. high spelling skills, HR = 2.02, 95% CI 1.16–3.51; low vs. high reading skills, HR = 2.01, 95% CI 1.27–3.17). Associations were still evident, especially for verbal intelligence and reading skills, but hazard ratios were attenuated after adjusting for prenatal and sociodemographic factors at birth (verbal intelligence, HR = 1.97, 95% CI 1.03–3.78; spelling, HR = 1.61, 95% CI 0.90–2.88; reading, HR = 1.67, 95% CI 1.02–2.72). Conclusions: Childhood neurocognitive performance is associated with vulnerability to suicide mortality through middle‐adulthood, suggesting that there might be a cognitive diathesis for suicide originating in early childhood. Future studies should examine how multiple domains of childhood cognitive performance contribute to vulnerability to suicide risk, including by increasing risk for social and environmental factors that are associated not only with suicide but also with many types of psychiatric disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fibroids (hormonally responsive benign tumors) often undergo volume changes in pregnancy. Because per- and polyfluoroalkyl substances (PFAS) disrupt hormonal signaling, they might affect fibroid growth. We assessed associations between PFAS and fibroid changes in pregnancy. METHODS: We analyzed seven PFAS, including perfluorohexanesulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), in plasma collected at 10–13 wk gestation from 2,621 women in the NICHD Fetal Growth Studies – Singletons cohort (2009–2013). Sonographers recorded fibroid number and volume of the three largest fibroids during up to six timed ultrasounds. Generalized linear models assessed associations of baseline log to the base 2 transformed log2-transformed PFAS and fibroid number, volume, and presence, and weighted quantile sum regression evaluated the PFAS mixture. Generalized linear mixed models with random intercepts assessed associations of PFAS and longitudinal fibroid number and total volume. Volume analyses were stratified by total volume at first visualization [equivalent to a fibroid less than 1 centimeter <1cm (small), 1 to less than 3 centimeters 1 to < 3cm (medium), or greater than or equal to 3 centimeters ≥ 3cm (large) in diameter]. RESULTS: Fibroid prevalence was 9.4% (푛 = 245 women). PFAS were not associated with changes in fibroid number, but were associated with volume trajectory, depending on baseline volume. Among women with small volume, PFAS were associated with fibroid growth: Each doubling in PFHxS and PFOS concentrations was associated with 3.6% [95% confidence interval (CI): 0.2, 7.0 and 5.2% (95% CI: -0.4, 11.1)] greater weekly fibroid growth, respectively. Among women with medium volume, PFAS were associated with shrinking: Doublings in PFOS, PFDA, and PFUnDA concentrations were associated with 1.9% (95% CI: 0.4, 3.3), 1.2% (95% CI: 0.1, 2.4), and 1.6% (95% CI: 0.4, 2.8) greater weekly fibroid volume reduction, respectively. DISCUSSION: Certain PFAS were associated with fibroid growth among women with small fibroids and decreases among women with medium fibroids. PFAS were not associated with fibroid prevalence or number; therefore, PFAS may influence prevalent fibroids rather than initiating fibroid development. [ABSTRACT FROM AUTHOR]

Study Question: Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?Summary Answer: Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy.What Is Known Already: Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments.Study Design, Size, Duration: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up.Participants/materials, Setting, Methods: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure.Main Results and the Role Of Chance: Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI).Limitations, Reasons For Caution: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association.Wider Implications Of the Findings: Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age.Study Funding/competing Interest(s): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: The American Academy of Pediatrics recommends that if parents choose to introduce juice, they wait until ≥12 months, citing concerns of obesity and dental caries.Objectives: We sought to identify correlates of early juice introduction (<6 months) and determine whether early introduction establishes a pattern of sugary beverage intake in childhood.Methods: Upstate KIDS is a prospective birth cohort study with follow-up through 7 years (n = 4989). The age of juice introduction was assessed from responses on periodic questionnaires from 4-18 months and categorized as <6,  6 to <12, and ≥12 months. Sociodemographic information was reported using vital records or maternal questionnaires. At 24, 30, and 36 months and 7 years, mothers reported their child's regular juice, soda, water, and milk intakes. The analysis was restricted to singletons and 1 randomly selected twin from each pair with information on juice introduction (n = 4067). We assessed associations of sociodemographic correlates with juice introduction using Cox proportional hazard models. The relations of juice introduction with beverage intake were evaluated using Poisson or logistic regression for adjusted risk ratios (aRR) or ORs, adjusting for sociodemographic covariates and total beverage intake.Results: Of the mothers, 25% and 74% introduced juice prior to 6 and 12 months, respectively. Younger maternal age; black or Hispanic race/ethnicity; lower educational attainment; Special Supplemental Nutrition Program for Women, Infants, and Children participation (yes); smoking during pregnancy; a higher pre-pregnancy BMI; a lower household income; and living in a townhouse/condominium or mobile home were associated with earlier juice introduction. Earlier juice introduction was related to a higher childhood juice intake, any soda intake, and lower water intake, holding total beverage intake constant [aRR, 1.5 (95% CI: 1.3-1.7; P-trend < 0.0001); adjusted OR 1.6 (95% CI: 1.0-2.4; P-trend = 0.01); aRR 0.9 (95% CI: 0.8-0.9; P-trend < 0.0001), respectively].Conclusions: Markers of lower socioeconomic status are strongly associated with earlier juice introduction, which, in turn, relates to sugary beverage intake in childhood, potentially replacing water. [ABSTRACT FROM AUTHOR]

Background: Severe iodine deficiency or excess during pregnancy can cause congenital hypothyroidism (CH). Iodine deficiency is common in pregnant women in the United States.Objectives: We conducted a nested case-control study in a cohort of ∼2.5 million births in California to determine whether iodine status is related to CH in a US population.Methods: Dried blood spots from 907 newborns with CH identified by newborn screening and 909 unaffected controls matched by month of birth were obtained from the California Newborn Screening Program to measure whole-blood iodine concentration. Iodine status was compared between cases and controls, and logistic regression was used to assess the association between CH status and blood iodine concentrations. Iodine status was also compared between cases and controls among infants treated in a neonatal intensive care unit (NICU) because CH has been reported in infants exposed to high levels of iodine in the NICU.Results: Blood iodine concentrations did not differ significantly between cases (median: 20.0 ng/mL; IQR: 12.1-29.8 ng/mL) and controls (median: 20.3 ng/mL; IQR: 12.5-30.9 ng/mL; P = 0.59). Neither extremely high nor extremely low blood iodine concentrations (1st, 5th, 95th, and 99th percentiles of the distribution) were more common in cases. Among infants treated in NICUs, however, cases had significantly (P = 0.01) higher iodine (median: 22.7 ng/mL; IQR: 16.4-32.1 ng/mL) compared with controls (median: 17.3 ng/mL; IQR: 8.3-26.6 ng/mL).Conclusions: CH cases did not have significantly higher or lower iodine in this population, which is reassuring given that maternal iodine deficiency is common in the United States. Among newborns in the NICU, CH cases had higher blood iodine concentrations compared with controls, suggesting that excess iodine exposure in the NICU could be causing CH. It may be beneficial to monitor iodine exposure from surgical procedures, imaging, and iodine-containing disinfectants and to consider non-iodine alternatives. [ABSTRACT FROM AUTHOR]

Background: The exposome is a novel research paradigm offering promise for understanding the complexity of human exposures, including endocrine-disrupting chemicals (EDCs) and pregnancy outcomes. The physiologically active state of pregnancy requires understanding temporal changes in EDCs to better inform the application of the exposome research paradigm and serve as the impetus for study.Methods: We randomly selected 50 healthy pregnant women with uncomplicated pregnancies from a pregnancy cohort who had available serum/urine samples in each trimester for measuring 144 persistent and 48 nonpersistent EDCs. We used unsupervised machine-learning techniques capable of handling hierarchical clustering of exposures to identify EDC patterns across pregnancy, and linear mixed-effects modeling with false-discovery rate correction to identify those that change over pregnancy trimesters. We estimated the percent variation in chemical concentrations accounted for by time (pregnancy trimester) using Akaike Information Criterion-based R methods.Results: Four chemical clusters comprising 80 compounds, of which six consistently increased, 63 consistently decreased, and 11 reflected inconsistent patterns over pregnancy. Overall, concentrations tended to decrease over pregnancy for persistent EDCs; a reverse pattern was seen for many nonpersistent chemicals. Explained variance was highest for five persistent chemicals: polybrominated diphenyl ethers #191 (51%) and #126 (47%), hexachlorobenzene (46%), p,p'-dichloro-diphenyl-dichloroethylene (46%), and o,p'-dichloro-diphenyl-dichloroethane (36%).Conclusions: Concentrations of many EDCs are not stable across pregnancy and reflect varying patterns depending on their persistency underscoring the importance of timed biospecimen collection. Analytic techniques are available for assessing temporal patterns of EDCs during pregnancy apart from physiologic changes. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine whether newborn concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) are associated with early childhood growth.Methods: A total of 1,954 singletons and 966 twins from the Upstate KIDS Study (born 2008-2010) were included in this study. Newborn dried blood spot concentrations of PFOS, PFOA, and BPA were quantified by liquid chromatography tandem mass spectrometry. Children's weight and height were reported from birth through 3 years of age. Repeated measures were modeled using generalized linear mixed models.Results: PFOS and PFOA were associated with lower BMI (-0.078 kg/m2 [-0.12 to -0.038] and -0.076 kg/m2 [-0.17 to -0.051] per 1 standard deviation increase in log PFOS and PFOA, respectively) and not with early obesity among singletons. Inconsistent associations were observed for twins. BPA levels were higher among neonates with a neonatal intensive care unit stay (P < 0.001), making associations difficult to interpret.Conclusions: Perfluorinated alkyl substances did not exhibit obesogenic associations with early measures of childhood growth. Blood-based BPA measures are limited by the nonpersistent nature of the chemical, and unknown sources from hospital settings may present only transient exposures. [ABSTRACT FROM AUTHOR]

Background: Although pregnancy loss affects one-third of pregnancies, the associated signs/symptoms have not been fully described. Given the dynamic nature of maternal physiologic adaptation to early pregnancy, we posited the relationships between signs/symptoms and subsequent loss would vary weekly.Methods: In a preconception cohort with daily follow-up, pregnancies were ascertained by self-administered sensitive home pregnancy tests on day of expected menses. We evaluated the effects of weekly time-varying signs/symptoms (including vaginal bleeding, lower abdominal cramping, and nausea and/or vomiting) on pregnancy loss <20 weeks in Cox proportional hazards models and calculated the week-specific probability of loss by the presence/absence of each sign/symptom.Results: Of 341 pregnancies ascertained by home pregnancy test, 95 (28%) ended in loss. Relationships between signs/symptoms and loss varied across time since first positive pregnancy test. In the first week following pregnancy confirmation, when many losses occurred, bleeding [hazard ratio (HR) 8.7, 95% confidence interval (CI) 4.7, 16.0] and cramping (HR 1.8, 95% CI 1.2, 2.7) were associated with loss even when accompanied by nausea and/or vomiting (HR 5.2, 95% CI 2.6, 10.5). After the second week, new relationships emerged with nausea and/or vomiting inversely associated (HR range 0.6-0.3, all 95% CI upper bounds <1.00) and bleeding no longer associated with loss. Probabilities of loss of ranged from 78% (95% CI 59%, 96%) with bleeding present in week 1 to 8% (95% CI 5%, 12%) with nausea/vomiting present in week 5.Conclusions: Relationships between signs/symptoms and pregnancy loss vary in early pregnancy possibly reflecting maternal physiologic response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human exposure to parabens and other antimicrobial chemicals is continual and pervasive. The hormone-disrupting properties of these environmental chemicals may adversely affect human reproduction. OBJECTIVE: We aimed to prospectively assess couples' urinary concentrations of antimicrobial chemicals in the context of fecundity, measured as time to pregnancy (TTP). METHODS: In a prospective cohort of 501 couples, we examined preconception urinary chemical concentrations of parabens, triclosan and triclorcarban in relation to TTP; chemical concentrations were modeled both continuously and in quartiles. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs) adjusting for a priori-defined confounders. In light of TTP being a couple-dependent outcome, both partner and couple-based exposure models were analyzed. In all models, FOR estimates < 1.0 denote diminished fecundity (longer TTP). RESULTS: Overall, 347 (69%) couples became pregnant. The highest quartile of female urinary methyl paraben (MP) concentrations relative to the lowest reflected a 34% reduction in fecundity (aFOR = 0.66; 95% CI: 0.45, 0.97) and remained so when accounting for couples' concentrations (aFOR = 0.63; 95% CI: 0.41, 0.96). Similar associations were observed between ethyl paraben (EP) and couple fecundity for both partner and couple-based models (p-trend = 0.02 and p-trend = 0.05, respectively). No associations were observed with couple fecundity when chemicals were modeled continuously. CONCLUSIONS: Higher quartiles of preconception urinary concentrations of MP and EP among female partners were associated with reduced couple fecundity in partner-specific and couple-based exposure models. CITATION: Smarr MM, Sundaram R, Honda M, Kannan K, Buck Louis GM. 2016. Urinary concentrations of parabens and other antimicrobial chemicals and their association with couples' fecundity. Environ Health Perspect 124:730-736; http://dx.doi.org/10.1289/EHP189 [ABSTRACT FROM AUTHOR]

Objectives We sought to examine whether there are systematic differences in ascertainment of preexisting maternal medical conditions and pregnancy complications from three common data sources used in epidemiologic research. Methods Diabetes mellitus, chronic hypertension, gestational diabetes mellitus (GDM), gestational hypertensive disorders (GHD), placental abruption and premature rupture of membranes (PROM) among 4821 pregnancies were identified via birth certificates, maternal self-report at approximately 4 months postpartum and by discharge codes from the Statewide Planning and Research Cooperative System (SPARCS), a mandatory New York State hospital reporting system. The kappa statistic ( k) was estimated to ascertain beyond chance agreement of outcomes between birth certificates with either maternal self-report or SPARCS. Results GHD was under-ascertained on birth certificates (5.7 %) and more frequently indicated by maternal report (11 %) and discharge data (8.2 %). PROM was indicated more on birth certificates (7.4 %) than maternal report (4.5 %) or discharge data (5.7 %). Confirmation across data sources for some outcomes varied by maternal age, race/ethnicity, prenatal care utilization, preterm delivery, parity, mode of delivery, infant sex, use of infertility treatment and for multiple births. Agreement between maternal report and discharge data with birth certificates was generally poor ( kappa < 0.4) to moderate (0.4 ≤ kappa < 0.75) but was excellent between discharge data and birth certificates for GDM among women who underwent infertility treatment ( kappa = 0.79, 95 % CI 0.74, 0.85). Conclusions for Practice Prevalence and agreement of conditions varied across sources. Condition-specific variations in reporting should be considered when designing studies that investigate associations between preexisting maternal medical and pregnancy-related conditions with health outcomes over the life-course. [ABSTRACT FROM AUTHOR]

Background: Perfluoroalkyl substances have been associated with changes in menstrual cycle characteristics and fecundity, when modeled separately. However, these outcomes are biologically related, and we evaluate their joint association with exposure to perfluoroalkyl substances.Methods: We recruited 501 couples from Michigan and Texas in 2005-2009 upon their discontinuing contraception and followed them until pregnancy or 12 months of trying. Female partners provided a serum sample on enrollment and completed daily journals on menstruation, intercourse, and pregnancy test results. We measured seven perfluoroalkyl substances in serum using liquid chromatography-tandem mass spectrometry. We assessed the association between perfluoroalkyl substances and menstrual cycle length using accelerated failure time models and between perfluoroalkyl substances and fecundity using a Bayesian joint modeling approach to incorporate cycle length.Results: Menstrual cycles were 3% longer comparing women in the second versus first tertile of perfluorodecanoate (PFDeA; acceleration factor [AF] = 1.03, 95% credible interval [CrI] = [1.00, 1.05]), but 2% shorter for women in the highest versus lowest tertile of perfluorooctanoic acid (PFOA; AF = 0.98, 95% CrI = [0.96, 1.00]). When accounting for cycle length, relevant covariates, and remaining perfluoroalkyl substances, the probability of pregnancy was lower for women in second versus first tertile of perfluorononanoate (PFNA; odds ratio [OR] = 0.6, 95% CrI = [0.4, 1.0]) although not when comparing the highest versus lowest (OR = 0.7, 95% CrI = [0.3, 1.1]) tertile.Conclusions: In this prospective cohort study, we observed associations between two perfluoroalkyl substances and menstrual cycle length changes, and between select perfluoroalkyl substances and diminished fecundity at some (but not all) concentrations. See video abstract at, http://links.lww.com/EDE/B136. [ABSTRACT FROM AUTHOR]

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]

Study Question: What is the relationship between couple's health and fecundity in a preconception cohort?Summary Answer: Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).What Is Already Known: The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.Study Design, Size, Duration: A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.Participants/materials, Settings, Methods: In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Main Results and the Role Of Chance: Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.Limitations, Reasons For Caution: The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.Wider Implications Of the Findings: The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Study Funding/competing Interests: Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Study Question: Is preconception urinary paracetamol (acetaminophen) associated with time-to-pregnancy (TTP)?Summary Answer: Higher urinary paracetamol concentrations among male partners were associated with a longer TTP.What Is Known Already: Paracetamol is a commonly used analgesic among women and men of all ages. As metabolites of select chemicals used in the manufacturing of polyurethane foam, dyes and various industrial products, as well as a common medicinal product, paracetamol and its primary metabolite p-aminophenol, are ubiquitous in the environment. Studies investigating the relationship between adult urinary concentrations of paracetamol and TTP are lacking.Study Design, Size, Duration: This prospective cohort included 501 couples discontinuing contraception for the purposes of attempting conception during the years 2005-2009 and residing in Michigan or Texas, USA.Participants/materials, Setting, Methods: Total urinary paracetamol, its metabolite para-aminophenol (p-aminophenol), and a summary measure of both urinary biomarkers were quantified by ultra-performance liquid chromatography coupled with an electrospray triple quadrupole mass spectrometry (UPLC-ESI-MS/MS). Female partners used the Clearblue® digital home test to confirm pregnancy. Cox's proportional odds models for discrete survival time were used to estimate fecundability odds ratios (FORs) and 95% confidence intervals (CIs), adjusting for age, body mass index (BMI), urinary creatinine, preconception smoking status, race/ethnicity and household income. Models were further adjusted for hypothyroidism and hypertension as an attempt to account for possible indications of paracetamol medication use. FOR estimates <1.0 denote a longer TTP (diminished fecundity). Models were performed to examine urinary concentrations of paracetamol as a continuous and variable or categorized into quartiles. In light of TTP being a couple-dependent outcome, models were first performed for females and males, modeled separately, and then modeled for couples with each partner's concentrations being adjusted for the other.Main Results and the Role Of Chance: Among the 501 enrolled couples, 347 (69%) had an human chorionic gonadotrophin confirmed pregnancy. Urinary concentrations of paracetamol were lowest among females and males who achieved pregnancy and p-aminophenol concentrations were lowest among those not achieving pregnancy. Urinary paracetamol concentrations were higher among female than male partners (Median = 26.6 and 13.2 ng/ml, respectively; P < 0.0001). After adjustment for age, BMI, urinary creatinine, preconception smoking status, race/ethnicity and household income, the highest quartile of male urinary paracetamol was associated with a longer TTP [FOR = 0.67; 95% CI = (0.47, 0.95)]. This association remained after adjustment for chronic health conditions, hypothyroidism and hypertension and female partner's urinary paracetamol concentration [FOR = 0.65; 95% CI = (0.45, 0.94)]. No associations were observed between female or male partners' urinary concentrations of paracetamol or of its metabolite p-aminophenol when urinary concentrations were modeled continuously.Limitations, Reasons For Caution: Only a single spot urine was available for analysis despite the short-lived nature of paracetamol. Additionally, participants were not asked to provide information on indication of use for paracetamol medications; any underlying conditions for the paracetamol use would have been potential confounders.Wider Implications Of the Findings: If corroborated with more robust studies, findings from our exploratory analysis may have both clinical and public health relevance among reproductive aged individuals, including those trying for pregnancy, given the prevalent use of paracetamol/acetaminophen medications and the ubiquitous nature of paracetamol in the environment.Study Funding/competing Interests: This research was supported by the National Institutes of Health, Intramural Research Program, and Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355; N01-HD-3-3356; NOH-HD-3-3358; HHSN27500001/HHSN27500001). None of the authors have any conflicts to declare. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We examined the longitudinal associations of age at achieving gross motor milestones and children's development in a US cohort of singletons and twins. METHODS: In the Upstate KIDS study, a population-based study of children born between 2008 and 2010, information on age at achievement of motor milestones and developmental skills was available in 599 children (314 singletons, 259 twins, and 26 triplets). Mothers reported their children's major motor milestones at ~4, 8, 12, 18, and 24 months. At age 4 years, children's development was clinically assessed by using the Battelle Developmental Inventory, Second Edition (BDI-2). Primary analyses by using multivariate linear regressions were conducted in singletons. We also examined the associations in twins. RESULTS: Later achievement of standing with assistance predicted lower BDI-2 scores in singletons in adjusted models (B per SD of age at achievement, -21.9 [95% confidence interval (CI), -41.5 to -2.2]). Post hoc analysis on age of standing with assistance showed that associations were driven by differences in adaptive skills (B = -5.3 [95% CI, -9.0 to -1.6]) and cognitive skills (B = -5.9 [95% CI, -11.5 to -0.4]). Analyses restricted to twins suggested no association between the age at achievement of milestones and total BDI-2 score after adjustment for gestational age and birth weight. CONCLUSIONS: This study provides evidence that the age of achieving motor milestones may be an important basis for various aspects of later child development. In twins, key predictors of later development (eg, perinatal factors) overshadow the predictive role of milestones in infancy. [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]

Background: While several studies have shown an association between environmental pollutants and diabetes among non-pregnant adults, few studies have prospectively assessed the association among pregnant women. We estimated the association between maternal pre-pregnancy levels of a polybrominated biphenyl (PBB 153) and 36 polychlorinated biphenyls (PCBs) with gestational diabetes (GDM).Methods: Data are from women (18-40 years) participating in a prospective cohort who achieved pregnancy lasting ≥24 weeks gestation and completed monthly pregnancy journals (n = 258). Women were recruited between 2005 and 2007 from 16 counties in Michigan and Texas. Women who ever reported a physician diagnosis of high blood glucose in monthly pregnancy journals were categorized as having gestational diabetes (n = 28; 10.9 %). Multivariable binary logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CIs).Results: There was no association between PBB 153 and GDM or any of the PCB congeners and GDM in unadjusted models. All associations remained non-significant with stepwise adjustment for age and waist-to-height ratio. Only with further adjustment for total serum lipids did the associations become significant, with lower levels of nine PCB congeners associated with GDM: 138, 153, 156, 167, 170, 172, 178, 180, and 194. The adjusted ORs for PCBs 170 and 180 were the strongest: 0.40 (0.18, 0.88) and 0.41 (0.19, 0.87), respectively.Conclusions: Pre-pregnancy levels of PCBs were not consistently associated with development of GDM in this prospective cohort of U.S. women. Interestingly, we found that although women with GDM had higher mean pre-pregnancy circulating lipid levels compared to women without GDM, they had lower wet weight circulating levels of many PCBs. More research is needed to understand the dynamic fluctuations of PCBs and other persistent organic pollutants between lipid compartments in women preparing to conceive and throughout pregnancy. [ABSTRACT FROM AUTHOR]

Background: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. Objectives: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Methods: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log–transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. Results: Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Conclusions: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. [ABSTRACT FROM AUTHOR]

Concern has arisen about benzophenone (BP) ultraviolet (UV) radiation filters, given their use in sunscreen and personal-care products and their reported estrogenic and antiandrogenic activity. We recruited 501 couples who were discontinuing use of contraceptives in order to become pregnant for the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (Michigan and Texas, 2005–2009). Couples provided urine specimens and completed daily journals until they either achieved pregnancy or had tried for 12 months. Women used fertility monitors to time sexual intercourse and digital pregnancy tests. Urinary concentrations of 5 UV filters (ng/mL) were determined using triple-quadrupole mass spectrometry: 2,4-dihydroxybenzophenone (also called BP-1); 2,2′,4,4′-tetrahydroxybenzophenone (BP-2); 2-hydroxy-4-methoxybenzophenone (BP-3); 2,2′-dihydroxy-4-methoxybenzophenone (BP-8); and 4-hydroxybenzophenone. Fecundability odds ratios were estimated for each UV filter (dichotomized at the 75th percentile) and adjusted for age, creatinine concentration, body mass index (weight (kg)/height (m)2), cotinine concentration, season, and site, while accounting for time off contraception. Separate models were fitted for each UV filter and partner; final models included partners' concentrations. Male partners' concentrations of BP-2 and 4-hydroxybenzophenone were associated with reduced fecundity in adjusted models (fecundability odds ratio (FOR) = 0.69 (95% confidence interval (CI): 0.50, 0.95) and FOR = 0.74 (95% CI: 0.54, 1.00), respectively). In models adjusting for both partners' concentrations, male BP-2 concentration remained associated with reduced fecundity (FOR = 0.69, 95% CI: 0.49, 0.97). These data suggest that male exposure to select UV filters may diminish couples' fecundity, resulting in a longer time to pregnancy. [ABSTRACT FROM PUBLISHER]

Background: Obesity is a growing public health problem among reproductive-aged women, with consequences for chronic disease risk and reproductive and obstetric morbidities. Evidence also suggests that body shape (i.e., regional fat distribution) may be independently associated with risk, yet it is not known if women adequately perceive their shape. This study aimed to assess the validity of self-reported body size and shape figure drawings when compared to anthropometric measures among reproductive-aged women. Methods: Self-reported body size was ascertained using the Stunkard nine-level figures and self-reported body shape using stylized pear, hourglass, rectangle, and apple figures. Anthropometry was performed by trained researchers. Body size and body mass index (BMI) were compared using Spearman's correlation coefficient. Fat distribution indicators were compared across body shapes for nonobese and obese women using analysis of variance (ANOVA) and Fisher's exact test. Percent agreement and kappa statistics were computed for apple and pear body shapes. Results: The 131 women studied were primarily Caucasian (81%), aged 32 years, with a mean BMI of 27.1 kg/m2 (range 16.6-52.8 kg/m2). The correlation between body size and BMI was 0.85 ( p<0.001). Among nonobese women, waist-to-hip ratios (WHR) were 0.75, 0.75, 0.80, and 0.82 for pear, hourglass, rectangle, and apple, respectively ( p<0.001). Comparing apples and pears, the percent agreement (kappa) for WHR≥0.80 was 83% (0.55). Conclusions: Self-reported size and shape were consistent with anthropometric measures commonly used to assess obesity and fat distribution, respectively. Self-reported body shape may be a useful proxy measure in addition to body size in large-scale surveys. [ABSTRACT FROM AUTHOR]

Background: An equivocal literature exists regarding the relation between persistent organochlorine pollutants (POPs) and endometriosis in women, with differences attributed to methodologies.Objectives: We assessed the association between POPs and the odds of an endometriosis diagnosis and the consistency of findings by biological medium and study cohort.Methods: Using a matched cohort design, we assembled an operative cohort of women 18–44 years of age undergoing laparoscopy or laparotomy at 14 participating clinical centers from 2007 to 2009 and a population-based cohort matched on age and residence within a 50-mile catchment area of the clinical centers. Endometriosis was defined as visualized disease in the operative cohort and as diagnosed by magnetic resonance imaging in the population cohort. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for each POP in relation to an endometriosis diagnosis, with separate models run for each medium (omental fat in the operative cohort, serum in both cohorts) and cohort. Adjusted models included age, body mass index, breast-feeding conditional on parity, cotinine, and lipids.Results: Concentrations were higher in omental fat than in serum for all POPs. In the operative cohort, γ-hexachlorocyclohexane (γ-HCH) was the only POP with a significant positive association with endometriosis [per 1-SD increase in log-transformed γ-HCH: adjusted OR (AOR) = 1.27; 95% CI: 1.01, 1.59]; β-HCH was the only significant predictor in the population cohort (per 1-SD increase in log-transformed β-HCH: AOR = 1.72; 95% CI: 1.09, 2.72) [ABSTRACT FROM AUTHOR]

Objective: Equivocal findings have been reported on the association between maternal depression and children's growth, possibly because of the limited attention to its disproportionate impact by child sex. The relationship between the timing of maternal depression and children's growth was assessed in a population-based prospective birth cohort, with particular attention to sex differences.Methods: The Upstate KIDS Study comprised 4,394 children followed through 3 years of age from 2008 to 2010. Maternal depression was measured antenatally by linkage with hospital discharge records before delivery and postnatally by depressive symptoms reported from questionnaires. Children's growth was measured by sex- and age-specific weight, height, weight for height, and BMI. Adjusted linear mixed effects models were used to estimate growth outcomes for the full sample and separately by plurality and sex.Results: Antenatal depression was associated with lower weight for age (-0.24 z score units; 95% confidence interval [CI]: -0.43, -0.05) and height for age (-0.26 z score units; 95% CI: -0.51, -0.02) among singleton boys. Postnatal depressive symptoms were associated with higher weight for height (0.21 z score units; 95% CI: 0.01, 0.42) among singleton girls.Conclusions: The findings of this study suggest that antenatal depression was associated with lower weight and smaller height only for boys, whereas postnatal depressive symptoms were associated with higher weight for height only for girls. The timing of depression and the mechanisms of sex-specific responses require further examination. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between preconception parental stress and the secondary sex ratio, defined as the ratio of males to females at birth.Design: A population-based preconception cohort.Setting: Not applicable.Patient(s): A total of 235 couples who were enrolled before conception in Michigan and Texas between 2005 and 2009 and who had a singleton birth during the follow-up period. Couples were interviewed separately at baseline to obtain information on perceived stress (Cohen's Perceived Stress Scale) and lifetime history of physician-diagnosed anxiety and/or mood disorders. Female partners were also trained to collect basal saliva samples for the measurement of salivary stress markers, alpha-amylase and cortisol.Intervention(s): None.Main Outcome Measure(s): Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) of a male birth for each stress marker.Result(s): After adjusting for potential confounders, we observed a 76% increase in the risk of fathering a male infant (RR 1.76; 95% confidence interval 1.17-2.65) in men diagnosed with anxiety disorders compared with those who were not diagnosed. When lifetime history of physician-diagnosed anxiety disorders was modeled jointly for the couple, the association was slightly strengthened (RR 2.03; 95% confidence interval 1.46-2.84).Conclusion(s): This prospective cohort study suggests that paternal lifetime history of physician-diagnosed anxiety disorders may be associated with an increase in the secondary sex ratio, resulting in an excess of male births. [ABSTRACT FROM AUTHOR]

Objective: To estimate pregnancy loss incidence in a contemporary cohort of couples whose lifestyles were measured during sensitive windows of reproduction to identify factors associated with pregnancy loss for the continual refinement of preconception guidance.Design: Prospective cohort with preconception enrollment.Setting: Sixteen counties in Michigan and Texas.Patient(s): Three hundred forty-four couples with a singleton pregnancy followed daily through 7 postconception weeks of gestation.Intervention(s): None. Couples daily recorded use of cigarettes, caffeinated and alcoholic beverages, and multivitamins. Women used fertility monitors for ovulation detection and digital pregnancy tests. Pregnancy loss was denoted by conversion to a negative pregnancy test, onset of menses, or clinical confirmation depending upon gestation. Using proportional hazards regression and accounting for right censoring, we estimated adjusted hazard ratios and 95% confidence intervals (aHR, 95% CI) for couples' lifestyles (cigarette smoking, alcoholic and caffeinated drinks, multivitamins) during three sensitive windows: preconception, early pregnancy, and periconception.Main Outcome Measure(s): Incidence and risk factors for pregnancy loss.Result(s): Ninety-eight of 344 (28%) women with a singleton pregnancy experienced an observed pregnancy loss. In the preconception window, loss was associated with female age ≥35 years (1.96, 1.13-3.38) accounting for couples' ages, women's and men's consumption of >2 daily caffeinated beverages (1.74, 1.07-2.81; and 1.73, 1.10-2.72, respectively), and women's vitamin adherence (0.45, 0.25-0.80). The findings were similar for lifestyle during the early pregnancy and periconception windows.Conclusion(s): Couples' preconception lifestyle factors were associated with pregnancy loss, although women's multivitamin adherence dramatically reduced risk. The findings support continual refinement and implementation of preconception guidance. [ABSTRACT FROM AUTHOR]

Purpose: Given reportedly high clustering but limited validity of retrospectively reported time-to-pregnancy (TTP), we assessed within-woman clustering for retrospectively reported TTPs alone and including gold-standard prospectively observed TTPs among women with 2 or more retrospectively reported and 1 or more prospectively observed TTPs. We further investigated whether past trying times inform future trying time among women with 1 or more retrospectively reported and 1 or more prospectively observed TTPs.Methods: Five hundred one couples attempting pregnancy were prospectively observed until human chorionic gonadotropin pregnancy or 12 months of trying. Women reported TTP for past planned pregnancies. Clustering as measured by the frailty variance was estimated using discrete Cox frailty models, adjusted for age, body mass index, smoking at each attempt. Utility of past attempts to inform future attempts was assessed with discrete Cox models and relative risk regression, adjusted for enrollment age, body mass index, smoking.Results: Seventy-five women with 2 or more prior pregnancies contributed 180 retrospective and 91 prospective TTPs for frailty modeling. Retrospectively reported TTP clustering was high (frailty variance = 0.89) but substantially lower when including prospectively observed TTPs (frailty variance = 0.42). Among 202 women with 1 or more prior pregnancies, past trying times did not inform future trying time.Conclusions: TTP recall rather than TTP may account for clustering. Past trying times may not inform future trying times. [ABSTRACT FROM AUTHOR]