Faculty Bibliography

Evidence increasingly confirms that synthetic chemicals disrupt the endocrine system and contribute to disease and disability across the lifespan. Despite a United Nations Environment Programme/WHO report affirmed by over 100 countries at the Fourth International Conference on Chemicals Management, 'manufactured doubt' continues to be cast as a cloud over rigorous, peer-reviewed and independently funded scientific data. This study describes the sources of doubt and their social costs, and suggested courses of action by policymakers to prevent disease and disability. The problem is largely based on the available data, which are all too limited. Rigorous testing programmes should not simply focus on oestrogen, androgen and thyroid. Tests should have proper statistical power. 'Good laboratory practice' (GLP) hardly represents a proper or even gold standard for laboratory studies of endocrine disruption. Studies should be evaluated with regard to the contamination of negative controls, responsiveness to positive controls and dissection techniques. Flaws in many GLP studies have been identified, yet regulatory agencies rely on these flawed studies. Peer-reviewed and unbiased research, rather than 'sound science', should be used to evaluate endocrine-disrupting chemicals.

BACKGROUND: Few studies have used GPS data to analyze the relationship between Walk Score, transportation choice and walking. Additionally, the influence of Walk Score is understudied using trips rather than individuals as statistical units. The purpose of this study is to examine associations at the trip level between Walk Score, transportation mode choice, and walking among Paris adults who were tracked with GPS receivers and accelerometers in the RECORD GPS Study. METHODS: In the RECORD GPS Study, 227 participants were tracked during seven days with GPS receivers and accelerometers. Participants were also surveyed with a GPS-based web mapping application on their activities and transportation modes for all trips (6969 trips). Walk Score, which calculates neighborhood walkability, was assessed for each origin and destination of every trip. Multilevel logistic and linear regression analyses were conducted to estimate associations between Walk Score and walking in the trip or accelerometry-assessed number of steps for each trip, after adjustment for individual/neighborhood characteristics. RESULTS: The mean overall Walk Scores for trip origins were 87.1 (SD = 14.4) and for trip destinations 87.1 (SD = 14.5). In adjusted trip-level associations between Walk Score and walking only in the trip, we found that a walkable neighborhood in the trip origin and trip destination was associated with increased odds of walking in the trip assessed in the survey. The odds of only walking in the trip were 3.48 (95% CI: 2.73 to 4.44) times higher when the Walk Score for the trip origin was "Walker's Paradise" compared to less walkable neighborhoods (Very/Car-Dependent or Somewhat Walkable), with an identical independent effect of trip destination Walk Score on walking. The number of steps per 10 min (as assessed with accelerometry) was cumulatively higher for trips both originating and ending in walkable neighborhoods (i.e., "Very Walkable"). CONCLUSIONS: Walkable neighborhoods were associated with increases in walking among adults in Paris, as documented at the trip level. Creating walkable neighborhoods (through neighborhood design increased commercial activity) may increase walking trips and, therefore, could be a relevant health promotion strategy to increase physical activity.

BACKGROUND: Dietary composition has been associated with sleep indexes. However, most of the evidence is based on cross-sectional data, and studies in young children are lacking. OBJECTIVE: The aim of this study was to explore the longitudinal associations of macronutrient composition of the diet with sleep duration and consolidation (number of awakenings) in infancy and early childhood. METHODS: The study was performed in 3465 children from the Generation R Study, a population-based cohort study in the Netherlands. Mothers reported their child's food intake at 13 mo of age by using a validated food-frequency questionnaire and their child's sleep patterns at 2 and 3 y of age. We used nutrient substitution models to assess the associations of relative macronutrient intakes with sleep indexes and adjusted the models for sociodemographic and lifestyle factors. RESULTS: Isocaloric substitution of fat intake by protein or carbohydrate in infancy was associated with longer total sleep duration at 2 but not 3 y of age. For each 5% increase in energy intake of either protein or carbohydrate at the expense of fat, sleep duration at 2 y of age was longer by 6 min (95% CI: 0.4, 12 min) and 4 min (95% CI: 2, 6 min), respectively. Further exploration of macronutrient subtypes indicated no consistent differences between saturated or unsaturated fat and that intake of plant compared with animal protein or Trp did not explain the association of higher total protein intake with longer sleep duration at 2 y of age. Replacing unsaturated with saturated fat was associated with 7 min (95% CI: -13, -1 min) shorter total sleep duration at 3 y of age. Macronutrient intakes were not associated with sleep consolidation. CONCLUSIONS: Our results suggest that the macronutrient composition of the diet is associated with sleep duration in young children. Future research should further study the causality of this association and explore the underlying mechanisms.

omega-3 and omega-6 polyunsaturated fatty acids are important for brain function and development. We examined whether maternal polyunsaturated fatty acid status during pregnancy affects risk of autistic traits in childhood. Within the Generation R cohort, we measured maternal plasma polyunsaturated fatty acid concentrations and the omega-3:omega-6 ratio in midpregnancy (Rotterdam, the Netherlands, 2001-2005). Child autistic traits at 6 years were assessed by using the Social Responsiveness Scale short form in 4,624 children. A lower maternal omega-3:omega-6 ratio during pregnancy was associated with more autistic traits in the offspring (beta = -0.008, 95% confidence interval: -0.016, -0.001). In particular, a higher total omega-6 and linoleic acid status were associated with more autistic traits (all P's < 0.05). Associations were independent of child intelligence, suggesting that the fatty acid distribution specifically affects the development of autistic traits in addition to general neurodevelopment. Maternal plasma omega-3 status was not associated with child autistic traits and, consistently, neither was prenatal dietary fish intake. Our study shows that a lower prenatal omega-3:omega-6 ratio is associated with more child autistic traits, which is largely accounted for by higher omega-6 instead of lower omega-3 status. These results suggest a biological pathway between maternal fatty acid intake during pregnancy and autistic traits in the offspring.

BACKGROUND: Exposure to elevated levels of inflammatory markers during pregnancy has been suggested as possible aetiologic factor in the occurrence of autism spectrum disorder (ASD). In this study, we investigated the prospective relation between maternal C-reactive protein (CRP) during early pregnancy and children's autistic traits in the general population. METHODS: In a large population-based cohort in the Netherlands, we measured maternal CRP levels before 18 weeks of gestation (N = 4165). Parents reported on their children's autistic traits at age 6 years using the Social Responsiveness Scale, and the Pervasive Developmental Problem scale. Regression models were used to examine the relation between maternal CRP levels and autistic traits in children. RESULTS: Compared with the reference group (CRP < 2.3 mg/L), elevated levels of CRP (>7.8 mg/L) in pregnant women were associated with higher Social Responsiveness Scale scores in children [beta = 0.055, 95% confidence interval (CI) 0.033, 0.078]; however, the effect was strongly attenuated after adjustment for several socioeconomic factors and in particular by maternal health-related factors including body mass index (fully adjusted model beta = 0.018, 95% CI -0.005, 0.042). We found no relation between maternal CRP levels and pervasive developmental problem. CONCLUSIONS: Our results suggest that the association between elevated levels of maternal CRP in pregnancy and autistic traits in children is confounded by maternal health-related and socioeconomic factors. Further studies are needed to explore whether other maternal inflammatory markers during pregnancy, as a response to maternal inflammation, are associated with the development of autistic traits in the offspring.

IMPORTANCE: An increasing percentage of births are conceived with assisted reproductive technology (ART) and other infertility treatment. Despite findings that such treatments may be associated with diminished gestation and birth size, scarce data exist regarding infertility treatments and children's development in the United States. OBJECTIVE: To assess the use and type of infertility treatment in relation to children's development through age 36 months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (conducted 2008-2014) that sampled based on infertility treatment and plurality. Included in the study were infants born between 2008 and 2010 in New York state (excluding New York City) whose parents completed developmental screening instruments through 36 months of age. A total of 4824 mothers (97% of 4989) completed 1 or more developmental screening instruments for 5841 children, including 1830 conceived with infertility treatment and 2074 twins. EXPOSURES: Maternal self-report of any infertility treatment was further categorized into ART and ovulation induction/intrauterine insemination. Assisted reproductive technology use was previously validated by linkage with the Society for Assisted Reproductive Technology-Clinical Outcome Reporting System. MAIN OUTCOMES AND MEASURES: Five developmental domains (fine motor, gross motor, communication, personal-social functioning, and problem-solving ability), as measured by the parental completion of the Ages and Stages Questionnaires at 4, 8, 12, 18, 24, 30, and 36 months of age. Generalized linear mixed modeling techniques estimated adjusted odds ratios (aORs) and 95% CIs for use and type of infertility treatment in relation to failing a developmental domain. Data were stratified by plurality and weighted for the sampling scheme. RESULTS: There were 1422 mothers (29.5%; mean [SD], age, 34.1 [5.2] years) who underwent infertility treatment. Infertility treatment was not associated with risk of their children failing any developmental domain (aOR, 1.33; 95% CI, 0.94-1.89). Assisted reproductive technology was associated with increased risk for failing any developmental domain but only when singletons and twins were evaluated together (aOR, 1.81; 95% CI, 1.21-2.72). Adjustment for birth weight further attenuated this estimate (aOR, 1.26; 95% CI, 0.82-1.93). After stratifying by plurality, type of treatment also was not significantly associated with failing any developmental domain for ovulation induction/intrauterine insemination (aOR, 1.00; 95% CI, 0.57-1.77 for singletons and aOR, 1.30; 95% CI, 0.76-2.21 for twins) or ART (aOR, 1.38; 95% CI, 0.78-2.43 for singletons and aOR, 1.58; 95% CI, 0.94-2.65 for twins). CONCLUSIONS AND RELEVANCE: After considering plurality, children's development through age 3 years was similar irrespective of infertility treatment or specific type. To our knowledge, these findings are among the first to focus on non-ART treatments in the United States.

Within a population-based study of 3356 children, we investigated whether infant neuromotor development was associated with cognition in early childhood. Neuromotor development was examined with an adapted version of Touwen's Neurodevelopmental Examination between 9 and 20 weeks. Parents rated their children's executive functioning at 4 years. At age 6 years, children performed intelligence and language comprehension tests, using Dutch test batteries. At age 6-9 years, neuropsychological functioning was assessed in 486 children using the validated NEPSY-II-NL test battery. We showed that less optimal neurodevelopment in infancy may predict poor mental rotation, immediate memory, shifting, and planning; but not nonverbal intelligence or language comprehension.

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.

BACKGROUND: Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of autism spectrum disorder. OBJECTIVES: We aimed to assess whether prenatal air pollution exposure is associated with childhood autistic traits in the general population. METHODS: Ours was a collaborative study of four European population-based birth/child cohorts-CATSS (Sweden), Generation R (the Netherlands), GASPII (Italy), and INMA (Spain). Nitrogen oxides (NO2, NOx) and particulate matter (PM) with diameters of