Showing papers by "Frederica P. Perera published in 2015"
TL;DR: In this cohort, Cesarean section and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity.
Abstract: Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother–child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33–154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8–98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.
381 citations
TL;DR: In utero bisphenol A exposure is used as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans and it is shown that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNFChanges in the cord blood of humans exposed to high maternal BPA levels in utero.
Abstract: Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain. We used in utero bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans. We show that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNF changes in the cord blood of humans exposed to high maternal BPA levels in utero. Our data suggest that BDNF DNA methylation in the blood may be used as a predictor of brain BDNF DNA methylation and gene expression as well as behavioral vulnerability induced by early-life environmental exposure. Because BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a novel biomarker for the early detection of psychopathology.
325 citations
TL;DR: The findings suggest that prenatal exposure to PAH air pollutants contributes to slower processing speed, attention-deficit/hyperactivity disorder symptoms, and externalizing problems in urban youth by disrupting the development of left hemisphere white matter, whereas postnatal PAH exposure contributes to additional disturbances in theDevelopment of white matter in dorsal prefrontal regions.
Abstract: Importance Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and neurotoxic environmental contaminants. Prenatal PAH exposure is associated with subsequent cognitive and behavioral disturbances in childhood. Objectives To identify the effects of prenatal PAH exposure on brain structure and to assess the cognitive and behavioral correlates of those abnormalities in school-age children. Design, Setting, and Participants Cross-sectional imaging study in a representative community-based cohort followed up prospectively from the fetal period to ages 7 to 9 years. The setting was urban community residences and an academic imaging center. Participants included a sample of 40 minority urban youth born to Latina (Dominican) or African American women. They were recruited between February 2, 1998, and March 17, 2006. Main Outcomes and Measures Morphological measures that index local volumes of the surface of the brain and of the white matter surface after cortical gray matter was removed. Results We detected a dose-response relationship between increased prenatal PAH exposure (measured in the third trimester but thought to index exposure for all of gestation) and reductions of the white matter surface in later childhood that were confined almost exclusively to the left hemisphere of the brain and that involved almost its entire surface. Reduced left hemisphere white matter was associated with slower information processing speed during intelligence testing and with more severe externalizing behavioral problems, including attention-deficit/hyperactivity disorder symptoms and conduct disorder problems. The magnitude of left hemisphere white matter disturbances mediated the significant association of PAH exposure with slower processing speed. In addition, measures of postnatal PAH exposure correlated with white matter surface measures in dorsal prefrontal regions bilaterally when controlling for prenatal PAH. Conclusions and Relevance Our findings suggest that prenatal exposure to PAH air pollutants contributes to slower processing speed, attention-deficit/hyperactivity disorder symptoms, and externalizing problems in urban youth by disrupting the development of left hemisphere white matter, whereas postnatal PAH exposure contributes to additional disturbances in the development of white matter in dorsal prefrontal regions.
272 citations
French Institute of Health and Medical Research1, Harvard University2, Katholieke Universiteit Leuven3, University of Rennes4, University of Wisconsin–Milwaukee5, Dartmouth College6, University of Occupational and Environmental Health Japan7, University of Rochester8, Columbia University9, University of Illinois at Chicago10, University of Cincinnati11, University of Missouri12, Boston University13, University of Queensland14, University of Turku15, University of Texas Health Science Center at Houston16
TL;DR: Vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects are highlighted.
Abstract: The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous “reprogramming” of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.
135 citations
TL;DR: Evidence is provided that PAHs are harmful to the developing fetal brain with effects extending through childhood, with implications for the academic success of the children.
Abstract: Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced by combus- tion of fossil fuel and other organic materials. Both experi- mental animal and human studies have reported the harmful impacts of PAH compounds on fetal growth and neurodevelopment, including verbal IQ of children. Here, we have assessed the association between cognitive function of children and prenatal PAH exposures. The study is part of an ongoing, longitudinal investigation of the health effects of prenatal exposure to air pollution on infants and children in Krakow, Poland. The subjects in this report included 170 children whose mothers were enrolled to the study in the first or second trimester of pregnancy whose cord blood were tested for PAH-DNA adducts and who were assessed at age 7 using the Wechsler Intelligence Scale for Children-Revised (WISC-R). The outcome of a priori interest was depressed verbal IQ index (DepVIQ), which is the difference between WISC-R performance and verbal IQ scores. Prenatal PAH exposure was measured by cord blood PAH-DNA adducts, an individual dosimeter, integrating exposure from various sources of exposure over the gestational period. Theestimated effect of prenatal PAH exposure on cognitive function was adjusted in multivariable regression for a set of potential confounders (child's gender, parity, maternal education, breastfeeding practice, environmental tobacco smoke (ETS), and postnatal PAH exposure).The prevalence of DepVIQ was significantly higher in children with detectable PAH-DNA adducts compared to those with undetectable adducts (13.7 vs. 4.4 %,). Binary multivariable regression documented that the relative risk of DepVIQ increased threefold with a ln-unit increase in cord blood adducts (relative risk (RR)=3.0, 95 % confidence interval (CI) 1.3-6.8). Postnatal PAH exposure also increased the risk of DepVIQ (RR=1.6, 95 % CI 1.1- 2.5). Long-term exclusive breastfeeding (at least 6 months) showed a protective effect (RR=0.3, 95 % CI 0.1-0.9). In conclusion, these results provide further evidence that PAHs are harmful to the developing fetal brain with effects extend- ing through childhood, with implications for the academic success of the children.
131 citations
TL;DR: BPA exposure may affect childhood behavioral outcomes in a sex-specific manner and differently depending on timing of exposure, as investigated in 7-9 year old minority children.
129 citations
TL;DR: In boys, higher maternal non-DEHP, but not DEHP, component scores were associated with lower BMI z-score, waist circumference, and fat mass in boys during early childhood, contrary to hypotheses.
Abstract: Background:Phthalate exposures are hypothesized to increase obesity; however, prior research has been largely cross-sectional.Objective:We evaluated associations between prenatal phthalate exposure...
93 citations
University of London1, National Institutes of Health2, Imperial College London3, Pompeu Fabra University4, University of Sydney5, Harvard University6, Food and Drug Administration7, University of Milan8, Washington University in St. Louis9, University of Cagliari10, University of Southampton11, Sapienza University of Rome12, Duke University13, Massey University14, University of California, Berkeley15, University of North Carolina at Chapel Hill16, University of Washington17, University of Exeter18, Louisiana State University19, University of Bremen20, Curtin University21, Université de Montréal22, Université Paris-Saclay23, University of Southern Denmark24, Karolinska Institutet25, Netherlands Cancer Institute26, Utrecht University27, German Cancer Research Center28, University of Paris29, University of California, Davis30, North Carolina State University31, Umeå University32, Seoul National University33, Dartmouth College34, National Institute of Occupational Health35, University of Massachusetts Lowell36, University of Caen Lower Normandy37, University of Cincinnati38, University of Iowa39, University of Copenhagen40, Australian National University41, University of Toronto42, World Health Organization43, University of Turin44, City University of New York45, Institut national de la recherche scientifique46, Columbia University47, George Washington University48, Autonomous University of Barcelona49, University of Guelph50, University of California, Los Angeles51, University of Amsterdam52, Uniformed Services University of the Health Sciences53, Texas A&M University54, University of Southern California55, University of Padua56, University of British Columbia57, Baylor College of Medicine58, Colorado State University59, University of Illinois at Chicago60, Emory University61, University of Texas Health Science Center at Houston62, Finnish Institute of Occupational Health63, Medical University of South Carolina64, American Cancer Society65, City of Hope National Medical Center66
TL;DR: Criticism of the IARC classification process are unconvincing, the procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence.
Abstract: BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also ...
77 citations
TL;DR: In this paper, a pooled analysis of four birth cohorts was conducted to identify the use of OOPs in the United States before 2001 and found that residential use was common before 2001.
Abstract: Background:Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001.Objectives:We conducted a pooled analysis of four birth c...
71 citations
TL;DR: Observed associations between high cord adducts and reduced IQ were significant only among the group of children whose mothers reported high material hardship, indicating the need for a multifaceted approach to prevention.
66 citations
TL;DR: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics.
Abstract: Background:Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent.Objectives:We pooled data from four cohorts to examine associati...
TL;DR: A positive trend between prenatal PBDE exposure and early childhood attention problems is demonstrated, and is consistent with previous research reporting associations between prenatalPBDE Exposure and disrupted child behaviors.
TL;DR: Long-term adiposity and PPWR in low-income African American and Dominican mothers were predicted by interacting effects of prepregnancy BMI and excessive GWG, and the provision of support for mothers to begin pregnancy at a healthy weight and to gain weight appropriately during pregnancy may have important lasting implications for weight-related health in this population.
TL;DR: The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure.
TL;DR: The results at age 2 suggest that prenatal exposure to a spectrum of PAH/aromatic pollutants may adversely affect early neurodevelopment, in part by reducing BDNF levels during the fetal period.
TL;DR: Prenatal exposure to airborne PAH showed a significant negative association with height growth, which was significantly decreased by 1.1cm at PAH level above 34.7 ng/m(3), and the height gain deficit associated with prenatal mercury exposure was not seen at birth, but the height growth was significantly slower at later age.
TL;DR: Vinyl flooring in the home may be an important source of children’s exposure to BBzP via indoor air, and indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations.
Abstract: Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations
TL;DR: Lower alpha-tocopherol, gamma-toc Haitianrol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure, and the importance of identifying modifiable factors for reducing harmful PAH effects is warranted.
TL;DR: Repeatedly high levels of urinary PAH metabolites during childhood may increase likelihood of sensitization to cockroach allergen in urban inner-city children at age 9 years.
TL;DR: Inexpensive and logistically feasible information could be used to estimate chronic personal exposure to PAH profiles, in lieu of costly and labor-intensive personal air monitoring at wide scale, using area-level meteorological or pollutant data.
TL;DR: The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting fromPAH exposure may be caused by the allergic inflammation within lung.
Abstract: Summary. The main purpose of the present study was to test the hypothesis that the depressed lung growth attributable to prenatal exposure to polycyclic aromatic hydrocarbons (PAH) may be modified by the intake of antihistamine medications. Individual prenatal PAH exposure was assessed by personal air monitoring in 176 children who were followed over nine years, in the course of which outdoor residential air monitoring, allergic skin tests for indoor allergens, lung function tests (FVC, FEV1, FEV05, and FEF25-75) were performed. The analysis with the General Estimated Equation (GEE) showed no association between prenatal PAH exposure and lung function in the group of children who were reported to be antihistamine users. However, in the group of antihistamine non-users all lung function tests except for FEF25-75 were significantly and inversely associated with prenatal airborne PAH exposure. The results of the study suggest that the intake of antihistamine medications in early childhood may inhibit the negative effect of fetal PAH exposure on lung growth and provides additional indirect evidence for the hypothesis that lung alterations in young children resulting from PAH exposure may be caused by the allergic