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To investigate the relationship of fibroids in pregnancy, preterm birth, and neonatal anthropometry. Pregnant women (n = 2578) in the National Institute of Child Health and Human Development Fetal Growth Studies–Singletons cohort had up to six ultrasounds across pregnancy. Sonographers recorded fibroid number and volume of the three largest fibroids. Trained personnel measured neonatal anthropometry. Linear and logistic regression compared neonatal anthropometry and pregnancy outcomes among pregnancies with versus without fibroids. Causal mediation analysis evaluated preterm birth as a mediator. Average birthweight did not differ by fibroid status. However, compared with pregnancies without fibroids, neonates from pregnancies with single fibroids had 0.3- (95% confidence interval [CI], 0.0, 0.5) cm larger head circumferences; those with multiple fibroids had 0.3- (95% CI, 0.0, 0.6) cm larger arm circumferences; and those with small fibroid volume had 0.7- (95% CI, 0.3, 1.2) cm larger head, 0.4- (95% CI, 0.0, 0.8) cm larger arm, and 0.7- (95% CI, 0.1, 1.3) cm larger thigh circumferences. Presence versus absence of fibroids was associated with 1.73–2.65 times higher odds of preterm birth. Differences in preterm birth did not explain fibroid-anthropometry results. We found no evidence that fibroids negatively impacted fetal growth; instead, fibroids were associated with increased head, arm, and thigh circumferences. ClinicalTrials.gov, NCT00912132. • Birthweight did not differ by fibroid status. • Based on neonatal measurements, fibroids did not appear to impede fetal growth. • Multiple and/or large fibroids were associated with higher odds of preterm birth. • Differences in preterm birth did not explain the fibroid-anthropometry results. [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]

Abstract Experimental studies suggest that prenatal exposure to endocrine disrupting chemicals interferes with developmental processes in the fetal brain. Yet, epidemiological evidence is inconclusive. In a birth cohort (2008–2010, upstate New York), we quantified concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) in stored newborn dried blood spots using liquid chromatography/tandem mass spectrometry. Mothers reported on children's behavior using the Strengths and Difficulties Questionnaire at age 7 (650 singletons and 138 twins). Difficulties in total behavior (i.e., emotional, conduct, hyperactivity, and peer problems) and prosocial behavior were classified using validated cut-offs. We used logistic regression with generalized estimating equations to estimate the odds of having difficulties per exposure category. In total, 111 children (12.1%) had total behavioral difficulties and 60 (6.5%) had difficulties in prosocial behavior. The median (interquartile range) of PFOS, PFOA, and BPA were 1.74 ng/ml (1.33), 1.12 ng/ml (0.96), and 7.93 ng/ml (10.79), respectively. Higher PFOS levels were associated with increased odds of having behavioral difficulties (OR per SD of log PFOS = 1.30, 95%CI: 1.03–1.65). We observed associations between PFOS in the highest relative to the lowest quartile and behavioral difficulties (OR for PFOS 1.14-1.74 = 1.65, 95%CI: 0.84–3.34; PFOS 1.75-2.47 = 1.73, 95%CI: 0.87–3.43; and PFOS >2.47 = 2.47, 95%CI: 1.29–4.72 compared to PFOS <1.41). The associations between higher concentrations of PFOS and behavioral difficulties at age 7 years were driven by problems in conduct and emotional symptoms. Higher PFOA levels were associated with difficulties in prosocial behavior (OR = 1.35, 95%CI: 1.03–1.75). There was an inverse association between BPA concentrations and difficulties in prosocial behavior but only in the 2nd and 4th quartiles. We found no interactions between sex and chemical concentrations. Increasing prenatal exposure to PFOS and PFOA, as reflected in neonatal concentrations, may pose risk for child behavioral difficulties. Graphical abstract Image 1 Highlights • We quantified concentrations of chemicals in newborn dried blood spots (DBS). • Higher PFOS levels were related to increased odds of behavioral difficulties. • Higher PFOA levels were associated with difficulties in prosocial behavior. • Newborn DBS can be used as a biospecimen for measurement of persistent chemicals. In children born between 2008 and 2010, we found that higher neonatal concentration of perfluorooctane sulfonate (PFOS) were associated with behavioral difficulties at age 7 years. [ABSTRACT FROM AUTHOR]

Objective: To estimate the association of pregnancy loss with common air pollutant exposure. Ambient air pollution exposure has been linked to adverse pregnancy outcomes, but few studies have investigated its relationship with pregnancy loss.Design: Prospective cohort study.Setting: Not applicable.Patient(s): A total of 343 singleton pregnancies in a multisite prospective cohort study with detailed protocols for ovulation and pregnancy testing.Intervention(s): None.Main Outcome Measure(s): Timing of incident pregnancy loss (from ovulation).Result(s): The incidence of pregnancy loss was 28% (n = 98). Pollutant levels at women's residences were estimated using modified Community Multiscale Air Quality models and averaged during the past 2 weeks (acute) and the whole pregnancy (chronic). Adjusted Cox proportional hazards models showed that an interquartile range increase in average whole pregnancy ozone (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.07-1.17) and particulate matter <2.5 μm (HR 1.13, 95% CI 1.03-1.24) concentrations were associated with faster time to pregnancy loss. Sulfate compounds also appeared to increase risk (HR 1.58, 95% CI 1.07-2.34). Last 2 weeks of exposures were not associated with loss.Conclusion(s): In a prospective cohort of couples trying to conceive, we found evidence that exposure to air pollution throughout pregnancy was associated with loss, but delineating specific periods of heightened vulnerability await larger preconception cohort studies with daily measured air quality. [ABSTRACT FROM AUTHOR]

Background: The relation between breastfeeding and early motor development is difficult to characterize because of the problems in existing studies such as incomplete control for confounding, retrospective assessment of infant feeding, and even the assessment of some motor skills too early. Objective: We sought to estimate associations between infant feeding and time to achieve major motor milestones in a US cohort. Design: The Upstate New York Infant Development Screening Program (Upstate KIDS Study) enrolled mothers who delivered live births in New York (2008-2010). Mothers of 4270 infants (boys: 51.7%) reported infant motor development at 4, 8, 12, 18, and 24 mo postpartum; information on infant feeding was reported at 4 mo. Accelerated failure time models were used to compare times to standing or walking across feeding categories while adjusting for parental characteristics, daycare, region, and infant plurality, sex, rapid weight gain, and baseline neurodevelopmental test results. Main models were stratified by preterm birth status. Results: The prevalence of exclusive breastfeeding in preterm infants was lower than in term infants at 4 mo postpartum (8% compared with 19%). After adjustment for confounders, term infants who were fed solids in addition to breast milk at 4 mo postpartum achieved both standing [acceleration factor (AF): 0.93; 95% CI: 0.87, 0.99] and walking (AF: 0.93; 95% CI: 0.88, 0.98) 7% faster than did infants who were exclusively breastfed, but these findings did not remain statistically significant after correction for multiple testing. We did not identify feeding-associated differences in motor milestone achievement in preterm infants. Conclusion: Our results suggest that differences in feeding likely do not translate into large changes in motor development. [ABSTRACT FROM AUTHOR]

We aimed to study the potential impact of proximity to major roadways on time-to-pregnancy and infertility in couples attempting pregnancy in the Longitudinal Investigation of Fertility and Environment (LIFE) study (2005–2009), a population-based, prospective cohort study. Couples attempting pregnancy (n = 500) were enrolled and followed prospectively until pregnancy or 12 months of trying and 393 couples (78%) had complete data and full follow-up. Time-to-pregnancy was based on a standard protocol using fertility monitors, tracking estrone-3-glucuonide and luteinizing hormone, and pregnancy test kits to detect human chorionic gonadotropin (hCG). The fecundability odds ratio (FOR) and 95% confidence interval (CI) were estimated using proportional odds models. Infertility was defined as 12 months of trying to conceive without an hCG pregnancy and the relative risk (RR) and 95% CI were estimated with log-binomial regression. Final models were adjusted for age, parity, study site, and salivary alpha-amylase, a stress marker. Infertile couples (53/393; 14%) tended to live closer to major roadways on average than fertile couples (689 m vs. 843 m, respectively) but the difference was not statistically significant. The likelihood of pregnancy was increased 3% for every 200 m further away the couples residence was from a major roadway (FOR = 1.03; CI = 1.01–1.06). Infertility also appeared elevated at moderate distances compared to 1000 m or greater, but estimates lacked precision. Our findings suggest that proximity to major roadways may be related to reductions in fecundity. Prospective data from larger populations is warranted to corroborate these findings. [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]

Objectives: To assess the association between age of juice introduction and child anthropometry after the American Academy of Pediatrics changed their guidelines in 2017 to recommend delaying juice introduction until at least 12 months of age (previously 6 months), citing concerns of weight gain.Study Design: Upstate KIDS is a prospective birth cohort with follow-up through 9 years of age. Juice introduction was assessed on parental questionnaires at 4-18 months and categorized as <6, 6-<12, and ≥12 months. Child height and weight were recorded at 2-3 and 7-9 years of age. Weight-, height-, and body mass index (BMI)-for-age and sex z scores were calculated using the Centers for Disease Control and Prevention reference. Overweight/obese and obese status were categorized as BMI-for-age z score ≥85th and ≥95th percentiles. Controlling for sociodemographic characteristics and parental BMI, we assessed the associations of age of juice introduction with child anthropometry.Results: Prevalence of childhood obesity was 16.4% at 2-3 (n = 1713) and 22.8% at 7-9 years of age (n = 1283). Juice introduction at <6 vs ≥12 months was associated with higher weight-for-age z score at 2-3 years of age (mean difference = 0.21; 95% CI 0.04-0.37). At 7-9 years of age, juice introduction at <6 vs ≥12 months was related to higher BMI-for-age (0.38; 0.12-0.64) and weight-for-age z scores (0.27; 0.06-0.49). Risk of developing overweight/obesity and obesity was 1.54 (0.99-2.38) and 2.17 (1.11-4.23) times higher among children with juice introduced at <6 months. No associations were found with juice introduced at 6-<12 vs ≥12 months.Conclusions: Risk of developing overweight/obesity or obesity is higher among children introduced to juice before 6 months of age compared with ≥12 months. [ABSTRACT FROM AUTHOR]

Objective To examine preconception serum concentrations of perfluorooctanoic acid (PFOA) and six other PFCs in relation to gestational diabetes (GDM) risk. Design Prospective cohort with longitudinal follow-up. Setting Not applicable. Patient(s) Among 501 women recruited upon discontinuing contraception for the purpose of becoming pregnant, 258 (51%) became pregnant and were eligible for the study, of which 28 (11%) reported having physician-diagnosed GDM during follow-up. Intervention(s) None. Main Outcome Measure(s) The odds ratios (ORs) and 95% confidence intervals (CIs) of GDM associated with each standard deviation (SD) increment of preconception serum PFOA concentration (ng/mL, log-transformed) and six other PFCs were estimated with the use of logistic regression after adjusting for age, prepregnancy body mass index, smoking, and parity conditional on gravidity. Result(s) Preconception geometric mean (95% CI) PFOA concentrations (in ng/mL) were higher for women with than without GDM (3.94 [3.15–4.93] vs. 3.07 [2.83–3.12], respectively). Each SD increment in PFOA was associated with a 1.87-fold increased GDM risk (adjusted OR 1.86 [95% CI 1.14–3.02]). A slightly increased risk associated with each SD increment for the six other PFCs was observed as well (all ORs >1.0, range 1.06–1.27), although the associations were not statistically significant. Conclusion(s) Our findings suggested that higher environmentally relevant concentrations of PFOA were significantly associated with an increased risk of GDM. If corroborated, these findings may be suggestive of a possible environmental etiology for GDM. [ABSTRACT FROM AUTHOR]

Objective: To determine whether feeding problems are indicators of developmental delay.Study Design: In this prospective longitudinal cohort study, mothers of 3597 children (49% female, 35% multiples) reported on their children's feeding problems and developmental delays (using the Ages and Stages Questionnaire [ASQ]) when children were age 18, 24, and 30 months. Average scores of feeding problems were computed at each age, as well as a categorical score indicating a persistently high number of feeding problems ≥90th percentile across time. The Battelle Developmental Inventory, Second Edition (BDI-2) was used to assess development in 5 domains for a subset of children at 4 years.Results: In adjusted analyses, feeding problems (per point increase) were increasingly associated with 6 ASQ domains from 18 months (OR, 1.30-1.98) to 24 months (OR, 2.07-2.69) to 30 months (OR, 3.90-5.64). Compared with children who never experienced feeding problems, children who experienced a high number of feeding problems at 1 or 2 time points were more than twice as likely to have a delay on all ASQ domains (OR, 2.10-2.50), and children who experienced a high number of feeding problems at all 3 time points were ≥4-fold more likely to have a delay on all ASQ domains (OR, 3.94-5.05). Children with 1-point higher feeding problems at 30 months scored 3-4 points lower in all BDI-2 domains at 4 years.Conclusions: Frequent feeding problems, especially those that persist into the third year, could be used to identify children at risk for developmental delay for more targeted screening. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between environmental chemicals and couple fecundity or time to pregnancy (TTP). Design: Prospective cohort. Setting: Communities of targeted populations with reported exposure. Patient(s): 501 couples recruited upon discontinuing contraception to become pregnant, 2005–2009. Intervention(s): None. Main Outcome Measure(s): Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) estimated for each partner’s chemical concentrations adjusted for age, body mass index, cotinine, creatinine, and research site while accounting for time off contraception. Result(s): Couples completed interviews and anthropometric assessments and provided the urine specimens for quantification of bisphenol A (BPA) and 14 phthalate metabolites, which were measured using high-performance liquid chromatography with electrospray triple-quadrupole mass spectrometer. Women recorded menstruation and pregnancy test results in daily journals. Couples were evaluated until a positive human-chorionic gonadotropin pregnancy test or 12 cycles without pregnancy. Neither female nor male BPA concentration was associated with TTP (FOR 0.98; 95% CI, 0.86, 1.13 and FOR 1.04; 95% CI, 0.91, 1.18, respectively). Men’s urinary concentrations of monomethyl, mono-n-butyl, and monobenzyl phthalates were associated with a longer TTP (FOR 0.80; 95% CI, 0.70, 0.93; FOR 0.82, 95% CI, 0.70, 0.97; and FOR 0.77, 95% CI, 0.65 0.92, respectively). Conclusion(s): Select male but not female phthalate exposures were associated with an approximately 20% reduction in fecundity, underscoring the importance of assessing both partners’ exposure to minimize erroneous conclusions. [Copyright &y& Elsevier]

Phytoestrogens have been associated with subtle hormonal changes, although effects on fecundity are unknown. Our objective was to evaluate the association between male and female urinary phytoestrogen (isoflavone and lignan) concentrations and time to pregnancy (TTP) in a population-based cohort of 501 couples desiring pregnancy and discontinuing contraception. Couples were followed for 12 mo or until pregnancy. Fecundability ORs (FORs) and 95%CIs were estimated after adjusting for age, body mass index, race, site, creatinine, supplement use, and physical activity in relation to female, male, and joint couple concentrations. Models included the phytoestrogen of interest and the sum of the remaining individual phytoestrogens. FORs <1 denote a longer TTP and FORs >1 a shorter TTP. Urinary lignan concentrations were higher, on average, among female partners of couples who became pregnant during the study compared with women who did not become pregnant (median enterodiol: 118 vs. 80 nmol/L; < 0.10; median P enterolactone: 990 vs. 412 nmol/L; < 0.05) and were associated with significantly shorter TTP in models based on both P individual and couples concentrations (couples' models: enterodiol FOR, 1.13; 95% CI: 1.02, 1.26; enterolactone FOR, 1.11; 95% CI: 1.01, 1.21). Male lignan concentrations were not associated with TTP, nor were isoflavone concentrations. Sensitivity analyses showed that associations observed are unlikely to be explained by potential unmeasured confounding by lifestyle or other nutrients. Our results suggest that female urinary lignan concentrations at levels characteristic of the U.S. population are associated with a shorter TTP among couples who are attempting to conceive, highlighting the importance of dietary influences on fecundity. [ABSTRACT FROM AUTHOR]

Objective: To assess semen parameters and couple fecundity as measured by time to pregnancy (TTP). Design: Observational prospective cohort with longitudinal measurement of TTP. Setting: Sixteen Michigan/Texas counties. Patient(s): A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided two samples. Intervention(s): None. Main Outcome Measure(s): Using prospectively measured TTP, fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for 36 individual semen quality parameters accounting for repeated semen samples, time off contraception, abstinence, enrollment site, and couples' ages, body mass indices, and serum cotinine concentrations. Result(s): In adjusted models, semen quality parameters were associated with significantly shorter TTP as measured by FORs >1: percent motility, strict and traditional morphology, sperm head width, elongation factor, and acrosome area. Significantly longer TTPs or FORs <1 were observed for morphologic categories amorphous and round sperm heads and neck/midpiece abnormalities. No semen quality parameters achieved significance when simultaneously modeling all other significant semen parameters and covariates, except for percent coiled tail when adjusting for sperm concentration (FOR 0.99; 95% CI 0.99–1.00). Male age was consistently associated with reduced couple fecundity (FOR 0.96; 95% CI 0.93–0.99), reflecting a longer TTP across all combined models. Female but not male body mass index also conferred a longer TTP (FOR 0.98; 95% CI 0.96–0.99). Conclusion(s): Several semen measures were significantly associated with TTP when modeled individually but not jointly and in the context of relevant couple-based covariates. [Copyright &y& Elsevier]

Objective: To assess the association between self-reported measures of stress, anxiety, depression, and related constructs and fecundity. Design: Prospective cohort study of women trying to conceive. Setting: United Kingdom. Patient(s): Three hundred thirty-nine women aged 18–40 years who were attempting to conceive. Intervention(s): Completed daily diaries for up to six cycles or until pregnancy was detected. For each cycle, stress biomarkers were measured and psychosocial questionnaires were completed. Main Outcome Measures(s): Fecundability odds ratios (FORs) and 95% confidence intervals were calculated using discrete time survival methods, and the day-specific probabilities of pregnancy were calculated using Bayesian statistical techniques. Result(s): Among the 339 women, 207 (61%) became pregnant during the study, 69 (20%) did not become pregnant, and 63 (19%) withdrew. After controlling for maternal age, parity, months trying to conceive before enrollment, smoking, caffeine use, and frequency of intercourse, we found no association between most psychosocial measures and FORs or the day-specific probabilities of pregnancy save for an increased FOR for women reporting higher versus lower levels of social support. Conclusion(s): Self-reported psychosocial stress, anxiety, and depression were not associated with fecundity. Any adverse effect of stress or psychological disturbance on fecundity does not appear to be detectable via the questionnaires administered. [ABSTRACT FROM AUTHOR]

Abstract: The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005–2009, couples (n =501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (μgL−1), lead (μgdL−1) and mercury (μgL−1) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63–0.97) and male lead (0.85; 95% CI 0.73–0.98) concentrations. When jointly modeling couples’ exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations. [Copyright &y& Elsevier]

Objective: To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment.Design: Clinical assessments in 2018-2019 in the Upstate KIDS cohort.Setting: Clinical sites in New York.Patient(s): Three hundred thirty-three singletons and 226 twins from 448 families.Intervention(s): Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits.Main Outcome Measure(s): The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children.Result(s): The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin.Conclusion(s): Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment.Clinical Trial Registration Number: ClinicalTrials.gov #NCT03106493. [ABSTRACT FROM AUTHOR]

Objectives: To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study.Study Design: Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression.Results: Compared with children of mothers with a BMI of <25, children whose mothers had BMI 25-30, 30-35, and ≥35 kg/m2 had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes.Conclusions: Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether deoxyribonucleic acid (DNA) methylation at birth and in childhood differ by conception using assisted reproductive technologies (ART) or ovulation induction compared with those in children conceived without fertility treatment.Design: Upstate KIDS is a matched exposure cohort which oversampled on newborns conceived by treatment.Setting: New York State (excluding New York City).Patient(s): This analysis included 855 newborns and 152 children at approximately 9 years of age.Intervention(s): None.Main Outcome Measure(s): DNA methylation levels were measured using the Illumina EPIC platform. Single CpG and regional analyses at imprinting genes were conducted.Result(s): Compared to no fertility treatment, ART was associated with lower mean DNA methylation levels at birth in 11 CpGs (located in/near SYCE1, SPRN, KIAA2013, MYO1D, GET1/WRB-SH4BGR, IGF1R, SORD, NECAB3/ACTL10, and GET1) and higher mean methylation level in 1 CpG (KLK4; all false discovery rate P<.05). The strongest association (cg17676129) was located at SYCE1, which codes for a synaptonemal complex that plays a role in meiosis and therefore infertility. This CpG remained associated with newborn hypomethylation when the analysis was limited to those conceived with ICSI, but this may be because of underlying male infertility. In addition, nine regions in maternally imprinted genes (IGF1R, PPIEL, SVOPL GNAS, L3MBTL, BLCAP, HYMAI/PLAGL1, SNU13, and MEST) were observed to have decreased mean DNA methylation levels among newborns conceived by ART. In childhood, hypomethylation of the maternally imprinted gene, GNAS, persisted. No CpGs or regions were associated with ovulation induction.Conclusion(s): ART but not ovulation induction was associated with hypomethylation at birth, but only one difference at an imprinting region appeared to persist in childhood. [ABSTRACT FROM AUTHOR]

Objective: To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems.Design: Prospective birth cohort study.Setting: Not applicable.Patient(s): A total of 1,915 mother-child dyads.Intervention(s): None.Main Outcome Measure(s): Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years.Result(s): Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively).Conclusion(s): Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records. [ABSTRACT FROM AUTHOR]

Maternal antenatal depression experienced around conception or during pregnancy may adversely affect child development. This study explores three potential mechanisms of the effects of antenatal depression on children's developmental delays at 2–3 years: gestational age of the child, continued depressive symptoms postnatally, and interrupted breastfeeding practices. Mothers (N = 2888) of 3450 children, including 2303 singletons and 1147 multiples from the Upstate KIDS cohort provided data. Linked hospital discharge data was combined with mothers' reports to identify women with moderate to severe antenatal depression. Gestational age was extracted from birth certificates. Mothers completed a depression screener at 4 months postpartum, reported about their breastfeeding practices from 4 to 12 months postpartum, and completed a developmental delay screener when children were 24, 30, and 36 months. In unadjusted path analysis models, mothers with antenatal depression had more postnatal depressive symptoms and breastfed fewer months, which translated into children being more likely to have developmental delays. Gestational age was not a mediator. Effects were similar across girls and boys and singletons and twins, and largely held when adjusting for covariates. Main limitations were the relatively advantaged sample and reliance on maternal report. Maternal antenatal depression may impact child development through continued depressive symptoms in the postpartum period and through reduced breastfeeding duration suggesting additional targets for intervention. • This study explored 3 potential mechanisms of antenatal depression's effects on children's developmental delays at 2-3 years. • Associations were partially mediated by postnatal depression symptoms and breastfeeding duration, but not gestational age. • Models were similar across singletons and twins as well as girls and boys. • Beyond treating depression, this study suggests that breastfeeding may be a viable target for intervention. [ABSTRACT FROM AUTHOR]

Environmental exposure to metals and metalloids is associated with pregnancy loss in some but not all studies. We assessed arsenic, cadmium, mercury, and lead concentrations in 501 couples upon trying for pregnancy and followed them throughout pregnancy to estimate the risk of incident pregnancy loss. Using Cox proportional hazard models, we estimated hazard ratios (HR) and 95% confidence intervals (CIs) for pregnancy loss after covariate adjustment for each partner modeled individually then we jointly modeled both partners’ concentrations. Incidence of pregnancy loss was 28%. In individual partner models, the highest adjusted HRs were observed for female and male blood cadmium (HR = 1.08; CI 0.81, 1.44; HR = 1.09; 95% CI 0.84, 1.41, respectively). In couple based models, neither partner’s blood cadmium concentrations were associated with loss (HR = 1.01; 95% CI 0.75, 1.37; HR = 0.92; CI 0.68, 1.25, respectively). We observed no evidence of a significant relation between metal(loids) at these environmentally relevant concentrations and pregnancy loss. [ABSTRACT FROM AUTHOR]

Objective: We sought to describe details of labor induction, including precursors and methods, and associated vaginal delivery rates. Study Design: This was a retrospective cohort study of 208,695 electronic medical records from 19 hospitals across the United States, 2002 through 2008. Results: Induction occurred in 42.9% of nulliparas and 31.8% of multiparas and elective or no recorded indication for induction at term occurred in 35.5% and 44.1%, respectively. Elective induction at term in multiparas was highly successful (vaginal delivery 97%) compared to nulliparas (76.2%). For all precursors, cesarean delivery was more common in nulliparas in the latent compared to active phase of labor. Regardless of method, vaginal delivery rates were higher with a ripe vs unripe cervix, particularly for multiparas (86.6-100%). Conclusion: Induction of labor was a common obstetric intervention. Selecting appropriate candidates and waiting longer for labor to progress into the active phase would make an impact on decreasing the national cesarean delivery rate. [ABSTRACT FROM AUTHOR]

Objective: We sought to prospectively measure women''s daily cigarette, alcohol, and caffeine use, while attempting pregnancy in relation to intentions to change. Study Design: This was a cohort comprising 90 women enrolled upon discontinuing contraception and followed up prospectively until pregnant. Women reported number of daily cigarettes, and alcoholic and caffeinated beverages for 459 menstrual cycles while attempting pregnancy. Results: A significant mean reduction in daily caffeinated drinks (estimate [EST] = −0.52; 95% confidence interval [CI], −0.70 to −0.33) was observed when compared to baseline usage. Intention to change was associated with a reduction in caffeinated drinks (EST = −0.32; 95% CI, −0.64 to 0.00), and with alcohol and cigarette usage from the first menstrual cycle (EST = −0.15; 95% CI, −0.28 to −0.02 and EST = −1.65; 95% CI, −3.12 to −0.19, respectively). Conclusion: A reduction in daily caffeine intake while attempting pregnancy was observed, but not in alcohol or cigarette use, underscoring the need for preconception guidance. [Copyright &y& Elsevier]

Single-pollutant models have linked prenatal PM 2.5 exposure to lower birthweight. However, analyzing air pollutant mixtures better captures pollutant interactions and total effects. Unfortunately, strong correlations between pollutants restrict traditional methods. We explored the association between exposure to a mixture of air pollutants during different gestational age windows of pregnancy and birthweight. We included 4,635 mother-infant dyads from a New York State birth cohort born 2008–2010. Air pollution data were sourced from the EPA's Community Multiscale Air Quality model and matched to the census tract centroid of each maternal home address. Birthweight and gestational age were extracted from vital records. We applied linear regression to study the association between prenatal exposure to PM 2.5 , PM 10 , NO X , SO 2 , and CO and birthweight during six sensitive windows. We then utilized Bayesian kernel machine regression to examine the non-linear effects and interactions within this five-pollutant mixture. Final models adjusted for maternal socio-demographics, infant characteristics, and seasonality. Single-pollutant linear regression models indicated that most pollutants were associated with a decrement in birthweight, specifically during the two-week window before birth. An interquartile range increase in PM 2.5 exposure (IQR: 3.3 µg/m3) from the median during this window correlated with a 34 g decrement in birthweight (95 % CI: −54, −14), followed by SO 2 (IQR: 2.0 ppb; β: −31), PM 10 (IQR: 4.6 µg/m3; β: −29), CO (IQR: 60.8 ppb; β: −27), and NO X (IQR: 7.9 ppb; β: −26). Multi-pollutant BKMR models revealed that PM 2.5 , NO X , and CO exposure were negatively and non-linearly linked with birthweight. As the five-pollutant mixture increased, birthweight decreased until the median level of exposure. Prenatal exposure to air pollutants, notably PM 2.5 , during the final two weeks of pregnancy may negatively impact birthweight. The non-linear relationships between air pollution and birthweight highlight the importance of studying pollutant mixtures and their interactions. [ABSTRACT FROM AUTHOR]

Objective: To study the association between salivary stress biomarkers and the secondary sex ratio. Design: Prospective, longitudinal cohort study. Setting: Community setting in the United Kingdom. Patient(s): On discontinuation of contraception for purposes of becoming pregnant, 338 women aged 18–40 years with complete data (90%) were followed until pregnant or up to six menstrual cycles. Intervention(s): None. Main Outcome Measure(s): Secondary sex ratio. Result(s): Human chorionic gonadotropin pregnancies were detected in 207 (61%) women of whom 130 (63%) delivered singleton infants with available gender data. The adjusted odds ratio for a male birth was decreased for women in the highest quartile (AOR = 0.26; 95% confidence interval = 0.09, 0.74) of salivary cortisol relative to women in the lowest quartile during cycle 1. An inverse relation was observed between α-amylase and the 2° sex ratio, though not statistically significant. Conclusion(s): Our findings are consistent with a reversal in the 2° sex ratio with increasing preconception salivary cortisol concentrations. This relation suggests that activation of the hypothalamus–pituitary–adrenal axis may have implications in sex allocation and requires further study. [ABSTRACT FROM AUTHOR]

Objective: To assess salivary stress biomarkers (cortisol and α-amylase) and female fecundity.Design: Prospective cohort design.Setting: United Kingdom.Patient(s): 274 women aged 18 to 40 years who were attempting pregnancy.Intervention(s): Observation for six cycles or until pregnancy: women collected basal saliva samples on day 6 of each cycle, and used fertility monitors to identify ovulation and pregnancy test kits for pregnancy detection.Main Outcome Measure(s): Salivary cortisol (μg/dL) and α-amylase (U/mL) concentration measurements; fecundity measured by time-to-pregnancy and the probability of pregnancy during the fertile window as estimated from discrete-time survival and Bayesian modeling techniques, respectively.Result(s): Alpha-amylase but not cortisol concentrations were negatively associated with fecundity in the first cycle (fecundity odds ratio=0.85; 95% confidence interval 0.67, 1.09) after adjusting for the couples' ages, intercourse frequency, and alcohol consumption. Statistically significant reductions in the probability of conception across the fertile window during the first cycle attempting pregnancy were observed for women whose salivary concentrations of α-amylase were in the upper quartiles in comparison with women in the lower quartiles (highest posterior density: -0.284; 95% interval -0.540, -0.029).Conclusion(s): Stress significantly reduced the probability of conception each day during the fertile window, possibly exerting its effect through the sympathetic medullar pathway. [ABSTRACT FROM AUTHOR]

Abstract: Trace exposures to metals may affect female reproductive health. To assess the relation between trace concentrations of blood metals and female fecundity, 99 non-pregnant women discontinuing contraception for the purpose of becoming pregnant were prospectively followed. Participants completed a baseline interview and daily diaries until pregnant, or up to 12 menstrual cycles at risk for pregnancy; home pregnancy test kits were used. For 80 women, whole blood specimens were analyzed for arsenic, cadmium, lead, magnesium, nickel, selenium and zinc using inductively coupled plasma mass spectrometry (ICP–MS). Time to pregnancy was estimated using Cox proportional hazards models for discrete time. Metal concentrations were generally within population reference intervals. Adjusted models suggest a 51.5% increase in the probability for pregnancy per 3.60μg/L increase in Mg (P =0.062), and a 27.7% decrease per 0.54μg/L increase in Zn (P =0.114). Findings indicate that Mg and Zn may impact female fecundity, but in varying directions. [Copyright &y& Elsevier]

Caffeine consumption has been equivocally associated with miscarriage, despite an absence of prospective longitudinal measurement of caffeine intake during sensitive windows of human development. In response to this critical data gap, we analyzed daily caffeine consumption while attempting pregnancy through 12 menstrual cycles at risk for pregnancy and found that caffeine consumption did not increase the risk or hazard of miscarriage, even after adjusting for relevant covariates. [Copyright &y& Elsevier]

Abstract Background Novel methodologies to quantify infant exposures to endocrine disrupting chemicals (EDCs) for population-based studies are needed. Objectives We used newborn dried blood spots to quantify three EDCs and their associations with infant outcomes in the Upstate KIDS Cohort. Methods We measured bisphenol A (BPA), perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in 2071 singleton and 1040 twin infants born to mothers in New York State. We log transformed concentrations after rescaling by their standard deviations and modeled each in relation to gestational age, birthweight, length, head circumference and Ponderal Index (PI) using linear regression techniques. All models were adjusted for maternal age, body mass index, education, infertility treatment and parity. Generalized estimating equations with robust standard errors were used to assess the associations for twins. Results Chemicals were largely quantified above the limits of detection (>99% for PFOS and PFOA; 90% for BPA). Overall, we observed no significant associations between PFASs and birth size irrespective of plurality of birth. However, among twins, BPA was associated with decreases in gestational age (adjusted β = −0.09 weeks; 95% Confidence Interval (CI): −0.16, −0.02) and birthweight (adjusted β = −32.52 g; 95% CI: −60.99, −4.05), head circumference (adjusted β = −0.18 cm; 95% CI: −0.38, −0.02) and increased PI in singletons (adjusted β = 0.02 cm; 95% CI: 0.004, 0.04). Conclusion We observed negative associations between BPA and birth size in twins. Our findings demonstrate the feasibility of newborn dried blood spots for quantifying neonatal exposure at the population level. Highlights • Used newborn dried blood spots to quantify BPA, PFOS and PFOA • Observed inverse association between BPA and birth size in twins • No observed association between BPA and birth size in singletons • No observed association with PFOS and PFOA and birth size, regardless of plurality [ABSTRACT FROM AUTHOR]

Abstract Background Intrauterine exposure to endocrine disrupting chemicals (EDCs) has been equivocally associated with birth weight, length and head circumference with limited attention to anthropometric endpoints such as umbilical circumference and limb lengths. Objective To explore 76 prenatal maternal plasma EDC concentrations in a healthy obstetric cohort and 7 neonatal anthropometric endpoints by maternal race/ethnicity. Methods The study cohort comprised 2106 (564 White, 549 Black, 590 Hispanic, 403 Asian) healthy pregnant women recruited from 12 U.S. clinical sites between 2009 and 2012 who were followed through delivery. Neonates underwent standardized anthropometric assessment (weight, length, head and umbilical circumference, and mid- upper arm and thigh length). Plasma EDC concentrations were quantified using high resolution gas chromatography-high resolution mass spectrometry and liquid chromatography-tandem mass spectrometry. EDCs were log-transformed and rescaled by their deviations (SD) when modeled relative to neonatal endpoints using linear regression adjusting for age, education, pre-pregnancy body mass index (BMI), serum cotinine, serum lipids for lipophilic chemicals, and a race/ethnicity interaction term; p-values had false discovery rate correction (<0.05). Results The cohort comprised women aged 28 (SD = 5) years with normal BMIs (23.6 kg/m2, SD = 3). Maternal EDC concentrations varied by self-identified race/ethnicity and neonatal outcomes, though no specific EDC was consistently associated with neonatal anthropometric outcomes across racial/ethnic groups. For the overall cohort, perfluorooctanoic acid was negatively associated with birth length per SD increase in concentration (β = −0.23 cm; 95% CI −0.35, −0.10), while perfluorohexanesulfonic acid was negatively associated with umbilical circumference (β = −0.26 cm; 95% CI −0.40, −0.13), perfluorodecanoic acid with arm length (−0.09 cm; 95% CI −0.14, −0.04), and PCBs congeners 118/106 (−0.12 cm; 95% CI −0.20, −0.04) and 146/161 (−0.14 cm; 95% CI −0.23, −0.05) with thigh length, as were 7 other poly-and-perfluorinated alkyl substances (PFASs). Conclusions Among healthy pregnant women with low risk antenatal profiles and relatively low EDC concentrations, reductions in umbilical circumference and bone lengths may be a sensitive marker of intrauterine EDC exposure, particularly for PFAS. Highlights • 76 endocrine disruptor chemicals (EDCs) were measured in cohort of pregnant women. • Newborns underwent standardized neonatal assessments at ≈1–2 days after birth. • EDC were not associated with gestation, birth weight or head circumference. • Reductions in umbilical circumference, birth length, arm and thigh length were found. • Poly-and-perfluorinated alkyl substances were most often associated with reductions. [ABSTRACT FROM AUTHOR]

To evaluate whether underlying infertility and mode of conception are associated with childhood behavioral disorders. Oversampling on fertility treatment exposure using vital records, the Upstate KIDS Study followed 2057 children (of 1754 mothers) from birth to 11 years. Type of fertility treatment and time to pregnancy (TTP) were self-reported. Mothers completed annual questionnaires reporting symptomology, diagnoses, and medications at 7–11 years of age. The information identified children with probable attention-deficit/hyperactivity disorder, anxiety or depression, and conduct or oppositional defiant disorders. We estimated adjusted relative risks (aRR) for disorders by underlying infertility (TTP > 12 months) or treatment exposure groups compared to children born to parents with TTP ≤ 12 months. Children conceived with fertility treatment (34%) did not have an increased risk of attention-deficit/hyperactivity disorder (aRR): 1.21; 95% CI: 0.88, 1.65), or conduct or oppositional defiant disorders (aRR: 1.31; 0.91, 1.86), but did have an increased risk of anxiety or depression (aRR: 1.63; 1.18, 2.24), which remained elevated even after adjusting for parental mood disorders (aRR: 1.40; 0.99, 1.96). Underlying infertility without the use of treatment was also associated with a risk of anxiety or depression (aRR: 1.82; 95% CI: 0.96, 3.43). Underlying infertility or its treatment was not associated with risk of attention-deficit/hyperactivity disorder. Observations of increased anxiety or depression require replication. [ABSTRACT FROM AUTHOR]