Children ’ s Environment in Brazil : From Domestic ( Indoor ) to Regional Threats

In the globalized world of the 21st century, most of the child population has been stimulated by many opportunities and challenges, but they have also found huge barriers in relation to their health, development and well-being in the form of environmental threats [1]. According to international data, in 2015, approximately 5.9 million children died under age five, in an estimated rate of 16,000 deaths per day, mostly from diseases that are promptly preventable and treatable with tested, costeffective and quality-delivered interventions [2]. The number of under-five deaths over the past two decades is astounding: between 1990 and 2015, nearly 230 million children worldwide died before their fifth birthday, more than today’s population of Brazil, the world’s fifth most populous country [3]. But the good news is that nowadays, under-five mortality rate has decreased. In 2015, there were 19,000 fewer deaths of children in this age group than in 1990, the reference year for measuring progress [2].


Introduction
In the globalized world of the 21st century, most of the child population has been stimulated by many opportunities and challenges, but they have also found huge barriers in relation to their health, development and well-being in the form of environmental threats [1].According to international data, in 2015, approximately 5.9 million children died under age five, in an estimated rate of 16,000 deaths per day, mostly from diseases that are promptly preventable and treatable with tested, costeffective and quality-delivered interventions [2].The number of under-five deaths over the past two decades is astounding: between 1990 and 2015, nearly 230 million children worldwide died before their fifth birthday, more than today's population of Brazil, the world's fifth most populous country [3].But the good news is that nowadays, under-five mortality rate has decreased.In 2015, there were 19,000 fewer deaths of children in this age group than in 1990, the reference year for measuring progress [2].The survival of every child is still an unpostponable priority and varies enormously depending on where a child was born and grows.Environmental risk factors, such as air, water and soil pollution, chemical exposures and climate change, contribute to more than 100 diseases and injuries [4].In low and mediumincome nations, the most commons environmental disorders, constituting major public health problem, are the lack of potable water and sanitation access, resulting in waterborne diseases, such as diarrhea [5] and lower respiratory tract infections.While in developed countries, the most prevalent diseases are allergy and asthma [6].Researchers have been analyzing the way the environment can change the expression of the genes and how that can cause diseases.Medications, pesticides, air pollutants, chemicals, heavy metals, hormones, nutrition products and behaviors can change the genetic expression by way of a huge amount of gene regulatory mechanisms [7].
Important information regarding accidental poisonings and intoxications is that children, by nature, are curious, and can open, eat and drink what adults know to be dangerous agents.Parents and caretakers, by negligence or lack of information, keep medications and domestic products in inappropriate places, underestimating what children can do.The habit of selfmedication can lead to a higher intake of medication, which makes it easier for those agents to reach domiciles, where children can potentially get access and be poisoned by them [8].
Pollution in the indoor environment is a multifaceted mixture of agents migrating indoors from the outdoor air in addition to agents generated by indoor sources [9].Tobacco smoke is a threat to children's health with adverse effects on their pulmonary function [10,11].The smoke of tobacco is full of exogenous mutagenic and cancerous agents [12,13].
Data from the WHO [14] shows secondary domestic pollution due to the burning of solid fuel (wood, coal, manure, crop residue) on fires or traditional stoves as one of the top ten risks to health in the world, affecting children directly.The inefficient burn of those solid fuels releases a dangerous mixture of thousands of substances such as particulate matter, carbon monoxide, nitrous oxide, sulfuric oxides, formaldehyde, hydrocarbons and polycyclic organic matter, which includes carcinogenic substances such as benzopyrene [15].The amount of smoke women and their young children inhale can be equal to that of two packs of cigarettes a day [16].Through the air, the smoke from forest fires is made up of gases, such as water vapor, molecular nitrogen, SO 2 , CO, CO 2 , CH 4 , among others, and ash micro particles [17].The total suspended particulate matter, inhalable particulate matter and nitrogen dioxide can cause, on children who live near where fires take place, side effects through a combination of harm caused by heat, pulmonary irritation, oxygen deprivation (asphyxia) and poisoning [17].
The contamination of the environment by chemical agents (aluminum, mercury, pesticides, petroleum hydrocarbons, silver, vinyl chloride, arsenic, cyanide, benzopyrene) resulting from untreated water; industrial activities; mineral exploration and agriculture can be responsible for the increase in congenital malformations, asthma, cancer, disruption of the endocrine system, neurological and behavioral disorders in children [18,19].The physical agents that can also present hazards to children's health are sediment resuspension, turbidity, corrosive materials, and water offensive odors and incompatible color [20].This vulnerability children have to environmental hazards occurs because the child population is a peculiar demographic group that shows very specific physiological characteristics: it is during the early childhood that several biological systems, like the brain, lung structure and the immune system develop and mature [9].Toxic gases can compromise pulmonary function and neurodevelopment or exacerbate preexisting conditions, and children born prematurely can be more vulnerable to environmental hazards due to pulmonary immaturity at birth [21].Children ingest more water and food and breathe more air by body weight unit than adults.Infants, during the first 6 months, ingest seven times more water, and, at pre-school age (1 to 5 years of age), from three to four times more food by kilogram of body weight than the average adult [22].The intake of air of resting infants is twice as high in average adults [23].Peculiar habits, such as constantly putting their hand in their mouth [9] and playing and crawling in the ground also contribute to a higher exposure.Thus, agents present in the air, the water, the ground and in food have a higher probability to be absorbed by children than by adults.
Facing these facts, the authors conducted a review on the relationship between exposure to environmental pollutions and diseases in Brazilian children.Brazil is a large country, being the fifth in overall surface area, and has a wide regional diversity in terms of biomes and socioeconomic development.Several unfavorable environmental conditions and toxic substances present in several regions of Brazil, but independent of socioeconomic and cultural differences and occurring in rural and industrialized areas, are a threat to the lives of children, and a prolonged exposure could compromise the survival of their generations and others to come.The scope of the review covers indoor and outdoor pollutants for the entire Brazil from 1999 to 2013.The main knowledge and environmental issues acting on children health were identified and discussed, as well the remaining gaps.

Material and Methods
An ample bibliographic revision was carried out using the following electronic databases: MedLine, PubMed, Scielo, Lilacs and BDENF (Nursing Database) were used to retrieve relevant articles in the Brazilian literature published from 1999 to 2013.Besides the use of the aforementioned databases, a research was also carried out on the websites of organizations such as the World Health Organization -WHO, the United Nations Children's Emergency Fund -UNICEF the Pan American Health Organization -PAHO in order to update information found on the selected documents.Texts published on the website of Brazilian organizations of research in health and human geography such as Brazilian Institute of Geography and Statistic (IBGE) were also used.The databases were searched separately and then combined to eliminate duplication.
The search strategy involved terms as referred to Brazilian Virtual Health Library/Health Sciences Descriptors (DeCS) that includes, concomitantly, the Portuguese, the English and Spanish languages.The criteria for inclusion were: articles with data from research carried out exclusively in Brazil, published in national and evaluated according to criteria of journal classification in the QUALIS system of CAPES (Brazilian Federal Agency for the Improvement of Higher Education) (https://sucupira.capes.gov.br/) as A1-A2-B; international journals, available access to the full text of articles in the databases and whose methodology allowed for the discovery of evidence regarding the environmental influence in the health of children.The following types of papers were excluded: case study, dissertations, theses and guidelines.The research strategy included the following descriptors: "children health", "environmental risks", "health Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats

Geographic distribution
In order to have an overview of the geographic distribution of the studies, we considered for the analysis the five geographic regions of Brazil: North (N), Northeast (NE), Central-West (CW), Southeast (SE) and South (S).The N Region, takes up 45.25% of the absolute area of the country, has an estimated population of 17,186,877 people and is the region with the lowest population density [24].The NE Region has 18.2% of the country's area and an estimated population of 56,241,859 inhabitants [24].The CW Region has 18.86% of the country's area and an estimated population of 15,251,494 inhabitants [24].The SE Region has 10.85% of the country's area and an estimated population of 85,241,641 inhabitants.This region has the highest Gross Domestic Product -GDP of Brazil [22].The S Region has 6.77% of the country's area.It has an estimated population of 29,041,466 [24], and the one with the highest Human Development Index -HDI [25].It can be observed that 42% of the studies were carried out in the SE Region, which relates the richest region with the number of research.
The SE Region, predominate in the majority of papers.In the N Region, the majority of the articles deal with one subtheme of the R2 group, with relation to peculiar questions of the region, which comprehends most of the Amazon Basin, with its local particularities, such as mining, forest fires, and malaria cases, among others.The CW Region, despite holding the country's capital, has the fewest number of papers.Although Brazil is a federative union, few studies included two or more regions in their researches showing low number of integrated research on children's environment in the country.

Home Life
In this section, 22 articles related to two subthemes were selected: "unintentional ingestion of chemical compounds" and "home environmental pollution".

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.Lessa & Bochner (2008) [28] to identify the main therapeutic classes responsible for drug intoxications related to the hospitalization of children According to the authors, during early childhood, children are very curious and have no idea how dangerous toxic agents can be.The medication was the toxic agent most commonly found in the research with 77.7% of the studies.Included antiepileptic, sedative-hypnotic and antiparkinsonian drugs [28,29], bronchodilators [29], imidazole derivatives [33] and painkillers [32,34].There is also the hypothesis of medication poisoning through transplacental transmission and breast-feeding in children less than one month of age [28].
Pesticides were the second toxic agent (55.5%) found in the study [26,27,29,30,31], and poisoning was generally accidental in children and intentional in adolescents.In both cases the home was the locus of such occurrences.
Ease of access to those products was essential for selfharm and the adult's presence did not prevent the occurrence of intoxication [26,29,30,32].Vomiting and somnolence were considered a common clinical manifestation on children seen on hospital units [30] and infant deaths were reported as a complication of acute intoxication to toxic agents [28,29,34].
On the subtheme called "home environmental pollution", 13 articles were found (Tab.II).Articles demonstrated the impact of secondhand smoking on children's health since the intrauterine stage, affecting negatively anthropometric measurements (weight, length, and head circumference) of newborns [37,44].Parental smoking was also responsible for wheezing babies [35], ear infections and eye irritation [36] and history of respiratory diseases [42,45,47].In the case control studies, children exposed to smoking show higher risk to develop the abovementioned diseases than those who are not exposed [35,36,39,40].In addition, children living in crowded environments and poor housing conditions play a fundamental role in the causal chain of respiratory diseases [38,42,46].As well, the use of a wood stove for cooking was responsible for a higher occurrence of recurrent wheezing [41].

Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.  [44] to study the prevalence and risk factors for asthma in a cohort of children born in 1993 and followed up to the age of six years longitudinal 12.8% asthma / allergic rhinitis 6-7 y S Associated factors: female gender, non-white skin, asthma in the family, smoking during pregnancy and allergic rhinitis in children.
Carvalho & Pereira (2002) [45] to study the prevalence of respiratory morbidity among passive smoking children and to determine the effects of environmental tobacco smoke in the respiratory system cross-sectional wheezing / asthma / dyspnea / pneumonia < 5 y NE Associated factors: male gender, parental smoking and respiratory diseases history.
Regarding the respiratory tract the most frequent complaints were wheeze, dyspnea, asthma, bronchitis or pneumonia and rhinitis.Prietsch et al. (2002) [46] to study the prevalence of acute disease of the lower airways and the role of the domestic environment and maternal smoking cross-sectional acute resp.disease < 5 y S Associated factors: similar distribution according to age and sex, passive smoking, living in crowded environments and poor housing conditions Pereira et al. (2000) [47] to determine the effects of second-hand smoke in the respiratory system in children cross-sectional 82% wheezing / dyspnea < 5 y NE Associated factors: male gender, environmental tobacco smoke: from 55.3% of passive smoking children in the study, 82% had respiratory problems.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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Social -Sanitation and Socio-environmental Factors
In the second block, 49 articles related to two subthemes were selected: "waterborne diseases" and the "prevalence of intestinal parasites".
Regarding the first subtheme, 22 articles were used (Tab.III).Researchers identified that precarious households [63,65], the lack of a sewage system [65,69], rudimentary lavatories, lack of a garbage collection [48,50,53,58,62] and the use of no potable water [60] are variables that influence the morbimortality rate of children under 5 years of age due to water-transmitted illnesses, like diarrhea [57].In this sence, cities with a low Human Development Index (HDI) have the highest mortality coefficients due to diarrheal disease [49] with 20% of the children in those regions having a deficit of > 2 standard-deviations for the height/ age index [55], leading these children to chronic malnutrition [62].Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.Strina et al. (2003) [64] to study the determinants of hygiene behavior and of its role in the transmission or prevention of diarrheal disease longitudinal 2.2% diarrheal disease < 5 y NE the prevalence of diarrhea among children for whom mainly unhygienic behavior and households with inadequate excreta disposal was 1.9 times that among children in the "mainly hygienic" group.Even though diarrheal diseases represent the second most common cause for hospital admissions in children under 5 years of age [48], researches have seen a considerable decrease in morbimortality caused by those illnesses.The factors that may have contributed to that decrease were the increase in purchasing power and consequently the betterment of living conditions [54] and the increase in the coverage of basic sanitation services [56,59].
Author's suggested that hepatitis A, another disease related to water-transmitted illnesses, is also present in area with poor environmental and sanitary conditions.The prevalence of positive anti-HAV among school children was significantly associated with low socioeconomic status [51,66,67], absence of both domestic water filter and sewage system [61] and indoor crowding [52].
Still in the Social research block, in the "prevalence of intestinal parasites", 27 articles were used (Tab.IV).The studies suggest that geo-helminths represent a major public health problem and are an important indicator of the sanitary conditions in which a certain population lives.The association between the prevalence of intestinal parasitic diseases with socioeconomic and environmental factors was reported in the most of researches like: children from slums [71] or residing in townships with a low HDI in the N and NE regions, especially in rural areas [74]; households with no proper waste management and no solid residue collection [78]; the unhealthy condition to which this population is subjected [72,87], with a direct relationship with low maternal schooling [81,95] and low income family [80,[85][86][87][88][89][90][91]95].The higher prevalence of Ascaris lumbricoides, Giardia duodenalis, Trichuris trichiura and hookworm infections in children living in contaminated environments [75,90,92,93] with inadequate daily caloric intake [94] may result in hospitalizations due to diarrheal disease [79], compromising their future anthropometric status [76,94].
On the other hand, studies suggested that a reduction of the prevalence of the parasites infections was possible by the increase of sewage systems [73,88,89,91,92], the use of a water filter [70] and the household being in an urban area [96].
The prevalence of parasitic diseases in children who go to daycare was another topic in this research.Daycares were found to contain giardiasis [82,83,95] and several helminths [77,84,86].The variable 'drinking water' showed a great influence on endoparasitic diseases in children of public institutions that ingested water without in-home treatment [81,95].Another variable, the relationship between the presence of helminth eggs in the water closet of kinder garden and the frequency of these eggs in the feces of their users were 15,4% positive.

Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.The overall prevalence was 51% of at least 1 parasite.There was a higher prevalence of intestinal parasites (63%) in children who attended day care than those who did not attend (41.4%) and the risk of infestation is 1.5 times higher.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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Regional -Regional environmental factors
In this segment, 56 articles were chosen and divided in three subthemes ranging from the "impacts of air pollution on respiratory diseases", "exposure to chemical micropollutants" and "exposure to other biological agents" on children's health.
For the first subtheme "impacts of air pollution on respiratory diseases", 28 articles were used (Tab.V).A significant association between risk of low birth weight and exposure to pollutants was found, like PM 10 , CO [98,112,118], SO 2 and O 3 [107].A research [108] also revealed a gradient of approximately 50% of increasing risk of early neonatal death with higher exposure to traffic-related air pollution, compared with those less exposed.
Several authors have explored the deleterious effect of outdoor air pollution on pediatric respiratory morbidity [117,119,124] with decrease in lung function [106], with increased risk for asthma [111] and pneumonia in children [99,113] in urban areas like the cities of São Paulo [100,114,122,123], Rio de Janeiro [105], Curitiba [119] and Sobral [104].Considering the lack of information on the air pollution effects on mortality in children's group, a study [121] showed the significant association between respiratory mortality in children and air pollution, in a city of SE Region.The estimated proportions of respiratory deaths attributed to CO, SO 2 , and PM 10 , when considered individually, were around 15%, 13%, and 7%, respectively.
Authors also observed a higher prevalence of Respiratory Diseases (RD) associated with seasonality.In the SE region [102] the highest number of hospital admissions happened in the peak of the transition between Summer and Fall, in the N and CO regions the hospitalization of RD was seen both in the dry [109,115] and in the wet season [110,116,120].
Another point of focus for the study was a relation between exposure to fine particulate matter from fire and the prevalence of RD in children.Andrade Filho et al. [97] noted that respiratory diseases may be more associated to meteorological conditions, especially humidity, than to exposure to aerosols from fires in the N region.Riguera et al. [101], while studying pollution from burning sugarcane and respiratory symptoms in school age children in the SE region, noted a higher frequency of rhinitis in the harvesting period for sugarcane.
Another point of focus for the study was a relation between exposure to fine particulate matter from fire and the prevalence of RD in children.Andrade Filho et al. [97] noted that respiratory diseases may be more associated to meteorological conditions, especially humidity, than to exposure to aerosols from fires in the N region.Riguera et al. [101], while studying pollution from burning sugarcane and respiratory symptoms in school age children in the SE region, noted a higher frequency of rhinitis in the harvesting period for sugarcane.[96] to establish a relationship between the presence of helminth eggs in the water closet elements and the frequency of these eggs in the feces of their users crosssectional

15.4% of infected children 2-6 y SE
The contamination levels in the children's feces was 37.8% and 16.1% in the toilets.The school which showed the lowest contamination by intestinal helminths (12% in feces and 0% in the toilets) was the one that was located in the most central area of the city.There was not significant relationship between the elements of water closets and user's feces contamination.

Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.Farhat et al. (2005) [114] to assess the effect of air pollution on pediatric respiratory morbidity crosssectional 15% hospitalization/ respiratory diseases < 13 y SE NO 2 was positively associated with all outcomes; .significantand positive associations between air pollution and respiratory morbidity in children were found.Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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Gouveia N.;
Fletcher T. ( 2000) [123] to investigate the short term effects of air pollution on the respiratory morbidity of children crosssectional > hospitalization < 5 y SE age: < 1 y; daily admissions of children in hospital for total respiratory disease and pneumonia showed significant increases associated with O 3 (5-8%), NO 2 (9%), and with PM 10 (9%).[124] to report the association between air pollution and pediatric respiratory emergency visits in the southeast region crosssectional 20% hospitalization/ respiratory emergency visits <13 y SE significant associations between the increase of respiratory emergency visits and air pollution were observed; the most robust associations were observed with PM 10 , and to a lesser extent with O 3; air pollution is a substantial pediatric health concern.

Lin et al. (1999)
In the subtheme "exposure to chemical micropollutants", 15 articles (Tab.VI) were identified.In the analyzed articles, pesticides, mercury, arsenic and lead were considered potential risk factors to children's health.
Researchers have suggested the relation between the use of agrochemicals and adverse events in children and adolescents.The findings showed that prenatal pesticide exposure is a risk factor to premature birth and inadequate maturation [128] and to some types of cancer in children.Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL) in young child were significantly associated with periconceptional exposure to pesticides (esbiothrin, tetramethrin, d-allethrin and d-phenothrin) [126].Curvo [125] analyzed the positive prevalence of morbimortality due to cancer in adolescents in cities of the CO region, where there was an increase in grain harvesting and 48.91% of agrochemicals used were shown to be carcinogenic.

Purpose Type of Study Health Effects Age Region Outcomes
Curvo et al. ( 2013) [125] to analyze the association between the agricultural use of pesticides and cancer morbidity and mortality in children and adolescents longitudinal > morbidity > mortality <19 y CO male gender; the average use of pesticides in the counties showed a statistically significant association for both morbidity as for mortality for cancer children and adolescents, with 95% confidence interval.

Ferreira et al.
(2013) [126] to investigate the association between pesticide exposure during pregnancy and leukemia in children longitudinal 48.4% of AML/ 47.6%, of ALL < 2 y NE, CO, SE e S male gender; associations with ever use of pesticide exposure during pregnancy may be involved in the etiology of acute leukemia in children.

Dutra et al.
(2012) [127] to study a longitudinal assessment of mercury exposure in schoolchildren in an urban area longitudinal 1µg/g-8.22µg/ghair 10µg/L-60µg/L blood level at birth 8 -10 y N male gender; age: 8 y; there was a significant increase in blood mercury from 2004 to 2006 (p < 0.001), exposure through air pollution; the main exposure to mercury was during pregnancy.

Cremonese et al.
(2012) [128] to investigate potential relations between per capita pesticide consumption and adverse events in live born infants longitudinal > premature birth low Apgar score newborn S prenatal pesticide exposure is a risk factor for adverse pregnancy events such as premature birth and inadequate maturation.

Ferron et al.
(2012) [129] to estimate the prevalence of lead poisoning in children and to identify associated factors, as well as possible local sources of contamination crosssectional 16% blood lead levels ≥ 10.0 μg/dL 0 -5 y S male gender; age: 2,6 y; waste recylcing activities.; soil, and air pollution.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.Sakuma et al. (2010) [130] to assess children exposure to arsenic from environmental sources in a region of lead mining area crosssectional hight level of urinary arsenic in one group 7-14 y SE e S anthropic contamination may explain the higher urinary arsenic values.
Olympio et al. ( 2010) [131] to analyze household risk factors associated with high lead levels in surface dental enamel in adolescents living in poor neighborhoods crosssectional high dental enamel lead levels 14-18 y SE e S male gender; living in or close to a contaminated area and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries.[132] to identify the contamination sources and potential risk factors of the exposure in children from an economically deprived community crosssectional 40% Pb-S > 6μg/dL 5% Pb-S > 10 μg/dL 0-16 y SE male gender; the carcinogenic risk factor for ingestion was about 4 times; sociodemographic aspects: low income, sewer destiny, dust and contaminated soil.[138] to determine the blood lead levels in children living in an inactive lead foundry and to identify factors associated with differences in these levels crosssectional Pb : 17.1 ± 7. 3 mg/dL 1 -4 y NE visible presence of scum surrounding the home, family history of lead poisoning, and malnutrition; the environmental legacy of the lead foundry, represent a relevant risk factor for increased blood lead levels in children, especially those presenting pica.

Grandjean et al.
(1999) [139] to carry out cross-sectional studies in four comparable riverine communities that had exposure to methylmercury crosssectional 80% hairmercury > 10 microg/g 7 -12 y N the current mercury pollution seems sufficiently severe to cause adverse effects on brain development.
Another chemical contaminant related with Brazilian children's health living in several parts of the Amazon basin (N Region) has been mercury, used in the gold extraction process [133] and resulting in the contamination of freshwater fish with methylmercury [139].Children can be subjected to mercury exposure through: prenatal transfer across the placenta [134] with positive correlation with mother's frequency of fish consumption; breastfeeding, by ingesting breast milk containing mercury; and a diet rich in fish [127] with possible adverse effects on brain development [139].Riverine children presented higher exposure to methyl mercury (one organic form of mercury) as compared to other communities in the Brazilian Amazon [137], but in the clinical examination, no signs and symptoms were found that could jointly reflect a clinical picture characteristic of poisoning.
Concerning the prevalence of lead poisoning, studies found blood lead levels ≥ 10.0 μg/dl, in children, associated with waste recycling [129] and residing close proximity to a battery factory [136].Another study showed a strong association between adolescents with high dental enamel lead levels living in or close a contaminated area [131].In those three studies, the high lead levels seemed not affect the child population health.Another Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
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study showed a strong association between adolescents with high dental enamel lead levels living in or close a contaminated area [131].Sakuma et al. [130] reported that contamination from lead in a former mining area may explain the higher urinary arsenic values among the children living nearly, despite the median arsenic values do not warrant immediate health concern.Conversely, researchers suggested relations among important imbalances in cognition and language in early childhood with indices of contamination for lead up 10.0μg/dl to 45.40μg/dl [135], and also neurological risk factor of exposure to lead on dust and by ingestion, in children from an economically deprived community [132] especially in those presenting pica and malnutrition [138].
On the third subtheme "exposure to other biological agents", we used 13 articles (Tab.VII).Authors have studied the importance of early diagnosis of and correct treatment for dengue fever and malaria in endemic regions.The prevalence of dengue in children living in areas in the N Region [141,142], CO Region [145] and SE Region [147] have led to a disruption of routine health services, demanding further efforts towards providing technical training to health professionals working on the frontline of dengue treatment in children's patient care.As for malaria, researches had investigated children and adolescents who live in the N region [151,152].The lethality was 1.6% and besides the common symptoms of malaria triad (fever, chills and headache) they had among others like pallor, anemia, myalgia, vomiting and some degree of malnourishment [151], and there was a prevalence of malaria among adolescents [152].

Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats
Copyright: © 2017 Perlroth.N.H,et al.Another cause of illnesses in children related to regional socio-environmental factors are accidents that happen in area contiguous to the household.Authors detected anti-toxocara antibodies positive among schoolchildren living in a house with a yard and/or unpaved street and there was also an association between a seronegative ELISA test and previous treatment of pet dogs and/or cats with vermifuge [148].The occurrence of cutaneous leishmaniasis in children living in N and NE Region, suggested transmission in and around the house, and in a few cases, children were entering the forest [143] or presence of a family member with a history of these disease [146].Especially in rural areas in the SE Region where there are deforestation and residences near natural forest children can be stung by snakes and show clinical complications [149,150].Clinical researches [140,144] detected important ocular lesions caused by freshwater sponges species Drulia uruguayensis and Drulia ctenosclera, in school age children who swam in some rivers near their homes, in the Brazilian Amazon.These works revealed that freshwater sponge spicules may be a dangerous etiological agent of ocular pathology to kids that swim on those rivers.

Home Life
We can summarize, in relation to infant exposure to risk factors in the domicile lives that there are three direct threats: toxic substances, parental smoking and the burning of domiciliary biomass and living conditions at home.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.
home, in children younger than 5 years of age, was mostly due to household cleaning substances, pesticides and the inappropriate use of medicine.This result is very close to the conclusion of studies conducted by Mowry et al. [153], which suggests there is a need to create stronger national prevention campaigns focused on the inappropriate conditions in which products are purchased, on explaining about packaging of those agents, on raising awareness of the risks of the domestic environment and of the placement of the hazardous substances, which, in the research, were in the children's reach.
The present review has clearly shown the harmful effect of parent smoking on the respiratory health of the children and has identified three critical and biologically relevant windows of exposure to the adverse effect of second-hand smoking on children: i) in-utero, with a negative impact on the anthropometric measures of the newborn, confirmed also by Salihu and Wilson [154]; ii) in the first two years of life, when the respiratory tract infection rates are much higher and maternal smoking has a higher effect because the children stay a longer time at home in direct contact with the grownups [155]; iii) after the first two years, when respiratory diseases like bronchiolitis, asthma or pneumonia are more common, elevating the children morbidity.
Confirming that data, the research done by Gupta et al. [156] showed that, from over 40 studies, all but one have reported an increased risk among children whose parents smoke, and pooling the studies' results, children whose mothers smoke are estimated to have a 1.7-fold higher risk of these illnesses than children of nonsmoking mothers while paternal smoking alone causes a 1.3fold increase in risk.Heinrich [157], in an review of the influence of indoor factors in dwellings on the development of childhood asthma, corroborates the above data, suggesting that one of most consistent findings for the cause of asthma in childhood is related to exposure to environmental tobacco smoke.
But even worse than exposing children to tobacco smoke is contaminating them with third-hand smoking -THS [158], which according to Ramírez et al. [159] can cause changes to the DNA and cancer, as the nicotine residues provoke on lesions that break the molecule bonds responsible for transmitting the genetic code.In our research, we did not find any Brazilian study about so important theme.
Another important point to discuss is the smoke resulting from burning the domiciliary biomass and its repercussions on children's respiratory system.In Brazil, a country of vast socioeconomic contrasts, gas cylinders are expensive and/or hard to get, which makes the lower classes use firewood and coal in ovens.Data from the Tolmasquim & Guerreiro [160] shows that firewood is the second highest source of residential energy consumption in the country, accounting for 33.9% of all energy used in domestic supply.The WHO [14] reinforces that data by confirming that worldwide, around 3 billion people cook and heat their homes using open fires and simple stoves burning biomass like wood and coal.The most serious piece of data is that more than 50% of premature deaths among children under 5 are due to pneumonia caused by particulate matter (soot) inhaled from household air pollution [14].Even with such relevant information, we found only one research done on Brazil about this risk effects: the use of wood stove for cooking as a major factor associated for recurrent wheezing in children [41].

Social -Sanitation and Socio-environmental Factors
In this group, we worked with information about the prevalence of diseases children suffered that are related to sanitary conditions, like having no water supply waste.This data confirm the available scientific evidence that the dissemination of parasitosis and morbidity due to diarrhea are affected by environmental changes, high population concentration, poor hygiene and when faeces are disposed of improperly which can then contaminate food or other humans -person-to-person transmission [161].
Studies have shown that intestinal parasites like Ascaris lumbricoides and Trichuris trichiura are common in daycares, preschoolers and elementary school-age children.The CDC [162] corroborates that data by declaring that the Ascaris infection is one of the most common intestinal worm infections.It is found in association with poor personal hygiene, poor sanitation, and in places where human feces are used as fertilizer.According to the CDC [162], heavy infestations can affect the nutritional balance and harm the children's growth.Our study confirmed that alterations to the anthropometric state [76] and malnutrition of children can be secondary to parasitosis and are intimately associated to the insalubrious environment [62] especially in household that do not have a proper waste management and collection of solid residues [78].So improving the living conditions of the deprived population, as well as giving them access to a better healthcare are essential measures to cause a positive change in the situation shown above.
We have seen the general mortality and hospital morbidity rates due to diarrheic diseases in children under five years of age have been decreasing in Brazil.However, the Northern and Northeastern Regions, areas with the lower HDI in the country, still show the highest coefficients of mortality and the highest percentage of admittance of children under one year of age [49].Even though Brazil has almost 13% of all superficial hydric resources of the planet, it is a country where a vast number of people do not have bathroom inside the household, corresponding to 7.2 million people [163].Thirty four million people have no access to canalized water; 103 million people have no access to a waste disposal system, and only 38.7% of the generated waste is treated [164].The NE Region is where the lack of a sewerage system is most dire, and approximately 15.3 million people are affected by the lack of sanitation [165].The regional heterogeneity of the coefficients of mortality due to diarrhea reflects that socioeconomic and cultural inequality, as well as the difficulty the lowest classes have in getting access to healthcare and to sanitation.

Regional -Regional environmental factors
The relationship between the air pollution and the climatic variables has been a growing concern also on a regional level in Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.
Brazil due to the potential effects on human health, as it is also responsible for the increase of the number of the cases and the gravity of acute respiratory infection in children under five years of age.As a country with a tropical climate, throughout the year the weather is mild and, on occasion, very hot, with marked periods of rain and drought.The reduction of the relative humidity of the air below 30% is considered dangerous to the integrity of the airways, especially for a susceptible population [110].Some viruses have a seasonal behavior, with a higher frequency in the rain season and during sharp climatic changes, which also causes the precipitation of the particulate matter from the atmosphere in big cities, increasing the number of cases of pneumonia, asthma and bronchiolitis in vulnerable children.D' Amato et al. [166] confirm this data and report that climate change represents a massive direct threat to respiratory health by promoting or aggravating respiratory diseases or indirectly by increasing exposure to risk factors for respiratory diseases.More than 85% of all fires in Brazil during the dry season are concentrated in the Amazon region, accounting for a long-term source of emission of gases from the burning of biomasses during the dry season [167,168].Children and adolescents living in the Subequatorial Brazilian Amazon region exposed to high levels of PM 2.5 had toxicological risk quotients comparable to or higher than in children living in metropolitan regions where the PM 2.5 air pollution is above the recommended limits to human health [169].
In contrast to large cities in other countries where the main sources of aerosol particles are emissions linked to fossil fuel combustion [170], in Brazil, sugarcane burning contributed to 60% of the fine-mode aerosol mass [171] and can contribute to the aggravation of asthma and rhinitis episodes in susceptible children [101].
We have also found significant and positive relations between air pollution and respiratory morbidity in children who live in urban areas with a huge number of automobiles.The effect of the air pollution was detected in terms of emergency services and admittances in large and small cities in Brazil.Parker et al. [172], in a research conducted with North-American children, came to the same conclusion: the results provide evidence of adverse health effects for children living in areas with chronic exposure to higher levels of O 3 and PM 2.5 compared with children with lower exposures.
Another threat to the health of children that called our attention was the environmental contamination due to agrochemicals.In the last few years, Brazil has become the number one consumer of agrochemicals in the world [173] and increasingly dependent of such products and chemical fertilizers.In that sense, that exposure to agrochemicals and pesticides increase the prevalence of morbimortality due to cancer in the infant-juvenile population, and is also a possible risk factor for adverse effects during pregnancy, such as acute leukemia, premature parturition and improper maturation [125,126,128].Another perspective on this type of exposure is the study conducted by Rasier et al. [174] that reported exposure of the developing fetus or neonate to environmentally relevant concentrations of certain chemicals, among them endocrine disrupters, induces morphological, biochemical and/or physiological disorders in the brain and reproductive organs, by interfering with hormone actions.In our research, we did not find articles focusing this issue in the Brazilian children.
Conversely, exposure to environmental contaminants, including heavy metals, is a generalized problem relatively wellstudied in Brazil.The CDC [175] informs that today there are approximately half a million U.S. children ages 1-5 with blood lead levels above 5 µg/dl, the reference level at which CDC recommends public health actions be initiated.In our review, lead showed morbidity when the levels in the blood were higher than 10µg/dl [136] and could cause alterations in language acquisition [135].
We have also seen in the Amazon the presence of another toxic exposure agent, the mercury.When it transforms into methylmercury (MeHg) -its most toxic form -it can affect the neurological development of children that ingest contaminated fish during a prolonged period of time [137].According to Bose-O'Reilly et al. [176], even though epidemiologic studies in many countries report that fish intake is the single most influential predictor of blood or hair mercury levels, fish is a good dietary source of lean protein and omega-3 fatty acids, which are important for children to develop properly.So, for the authors, these beneficial effects may obscure adverse effects of methylmercury exposure.
According to literature, seroepidemiological surveys are an important research tool, especially in Public Health, because they allow the determination of the infection coefficient for a given pathology in a given population [148].In that sense, the subtheme "exposure to other biological agents" showed us the importance of epidemiological studies present in endemic regions in Brazil, where the socioeconomic conditions are worse, or by children activities in the forest around the houses.Studies on pediatric malaria are scarce [177] despite the increasing number of cases in children and adolescents due to malaria urbanization in various cities of the Amazon Region [152].
Concerning dengue fever, more than 2.5 billion people, in over 100 countries, are estimated to live in risk areas for the transmission of Aedes aegypty's vector [178].Our data survey had only 4 (30%) studies dedicated to the risk factors to children exposed to the dengue virus [141,142,145,147].The researches were conducted in the same Brazilian areas where today there are more cases of the zika virus and chikungunya caused by Aedes aegpty [179].
Besides being considered an international public health emergency with its epicenter in Brazil [180], the strong association, in time and place, between infections with the zika virus and a rise in detected cases of congenital malformations and neurological complications in newborns [181,182,183] of pregnant women who had contact with the vector highlights the importance of A. aegypty control.In January 2016, the Brazilian Ministry of Health [179] confirmed these data by disclosing Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

A Study on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia
Copyright: © 2016 Chauhan et al.
evidence that the zika virus crossed the placental barrier, transmitting the disease to the developing fetus [179].Nowadays, the elimination of this vector is becoming a health emergency in countries around the world.
An effective prevention policy for exposure to biological agents to be successful should effectually involve academic community, public health sectors and the society as a whole.

Conclusions
The scenery for children life including adverse effects of danger exposures in home life, lack of sanitation and other socio-environmental factors with regional hazards can generate an unfavorable environment for their health in several parts of Brazil.Studies conducted in all regions of the country have shown that the occurrence of preventable diseases from domestic to regional threats and their determinants in childhood years occur not by chance or at random in any community.It is possible to establish causal relations and, thus, define the protective factors to be considered in order to improve the quality of life of Brazilian children.Poverty and the lack of access to information on inherent healthcare practices that benefit the children population are key factors that must be changed to prevent pediatric diseases.
Other aspects arise when discussing how to improve the health of children all over Brazil.Considering the extensive area of the country and regional peculiarities, there is a need for government actions such as enforcing a tighter control on the use of pesticides and agrochemicals in general, monitoring air quality according to health standards and educational effort on parents and guardians in keeping children far from medicine, medicine cabinets and the like, disposal of waste in a safe and appropriately way, and others.Nonetheless, what can be learned from the studies analyzed is that the public sector as well as legal guardians must work together to reduce the number of preventable infant diseases and deaths due to environmental hazards.

Figure 1 :
Figure 1: Categorization of studies for analysis.

Table III : SOCIAL -SANITATION AND SOCIO-ENVIRONMENTAL FACTORS Waterborne diseases Reference Purpose Type of Study Health Efects Age Region Outcomes
Children's

on Incidence of Clinical Hypoxic Ischemic Encephalopathy Injury in Newborns with Perinatal Asphyxia Copyright: © 2016 Chauhan et al.
poor conditions of collective life in geographical areas; diarrhea accounted for a quarter of all admissions with a ratio of almost 33% in the urban inland and 35.3% in the rural inland.diarrheaprevalence fell from 9•2 days per childyear before the citywide sanitation intervention to 7•3 days per child-year afterwards.

Table IV : SOCIAL -SANITATION AND SOCIO-ENVIRONMENTAL FACTORS Prevalence of intestinal parasites
Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

Table V : REGIONAL-SPECIFIC ENVIRONMENTAL REGIONAL FACTORS Impacts of air pollution on respiratory diseases
Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats pediatr Child Care.2(2):1-28.

Children's Environment in Brazil: From Domestic (Indoor) to Regional Threats Copyright: © 2017 Perlroth.N.H,et al.
According to our research, the exposure to toxic agents at pediatr Child Care.2(2):1-28.