Mycotoxin Exposure and Children’s Health: Comparison
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Please note this is a comparison between Version 2 by Nora Tang and Version 1 by Paula Alvito.

The first 1000 days of life are very sensitive to any event that alters health programming, and they represent a window for intervention to improve population health. Pregnant women, fetuses, and infants are particularly vulnerable to exposure to food contaminated with mycotoxins. 

  • early-life exposure
  • mycotoxins
  • children
  • adverse pregnancy outcomes
  • baby foods
  • breast milk

1. Mycotoxins Exposure in Early-Life

Mycotoxins are natural low-molecular-weight metabolites produced by fungal species that can be toxic for humans and animals. Food ingestion is the main route of exposure to this substance group, but inhalation and dermal contact could also contribute, although to a lesser extent. Mycotoxins are resistant to food processing and cooking practices and may be toxic even in low concentrations [1,2][1][2]. They occur all over the world and are closely associated with agricultural crops, particularly cereals, although they also appear in fruits, vegetables, and animal products (meat, dairy, eggs). They can affect single or multiple target organs, such as the liver, kidneys, and the immune system, with varying degrees of mutagenic, teratogenic, carcinogenic, and/or immunosuppressive potency [3,4][3][4]. Several mycotoxins may be carcinogenic to humans, as evaluated by the International Agency for Research on Cancer [5]. Under the climate change scenario, some fungal species might shift their geographical distribution in response to global warming, leading to changes in the pattern of mycotoxin occurrence and, thus, increasing human mycotoxin exposure [6,7][6][7].
Five major mycotoxins groups were reported to affect human health—aflatoxins (AFs) (mainly aflatoxin B1 (AFB1)), which cause liver cancer and have been implicated in child growth impairment and acute toxicoses; ochratoxins (OTAs) (mainly ochratoxin A), which are associated with renal diseases; fumonisins (FBs) (mainly fumonisin B1), which are associated with esophageal cancer and neural tube defects; trichothecenes (mainly desoxynivalenol (DON)), which are immunotoxic and cause gastroenteritis; and zearalenone (ZEN), which is known to have estrogenic effects [3,8][3][8]. Aspergillus mold strains produce AF and OTA, and Fusarium mold strains produce FBs, DON, and ZEN [9,10][9][10]. Primary food sources for AF include nuts, spices, corn (maize), cacao, coffee, rice, and cows’ milk. Cereals, coffee, and wine are a source of OTA, corn is a source of FB, wheat and barley are sources for DON, and wheat, barley, and sorghum are sources for ZEN [1,10][1][10]. Nevertheless, AFs and FBs are the most relevant mycotoxins that cause recognized harmful effects in fetuses and children [10,11][10][11].
Different countries throughout the world set regulations to protect consumers from food contaminated with mycotoxins. The Joint FAO/WHO Expert Committee on Food Additives reported the estimated mean dietary exposures to AFs, the most hepatotoxic substances known, in the ranges of 0.93–2.45, 3.5–180, and 0.3–53 ng/kg body weight/day for consumers in Europe, Africa, and in Asia, respectively. The contamination of food and feed by mycotoxins represents a serious health problem for humans and animals, as well as a considerable economic obstacle in most of the low- and middle-income countries [2].
Besides the free or parent mycotoxins (unchanged forms) that are regulated, several other non-regulated toxins are reported as modified and emerging mycotoxins, as well as a combination of mycotoxins that could impact human health [12[12][13][14],13,14], deserving special attention for their effects on pregnant women and young children. For all of the above reasons, understanding and monitoring human exposure to mycotoxins, particularly mothers and young children, is a key concern.
Children are much more vulnerable to the toxic effects of mycotoxins compared to adults because they have lower body mass and do not have a mature detoxification system [15,16][15][16]. The first 1000 days of life, the period from the fetal stage to 2 years old, is characterized by accelerated growth and developmental plasticity [17]. This early-life period is very sensitive to any event that alters the programming of the main body functions and represents a window for intervention to improve child and population health [18]. In this regard, pregnant women, fetuses, and infants are particularly vulnerable to exposure to environmental factors, particularly to food contaminants [18]. Mycotoxins from maternally-contaminated food can cross the placental barrier and affect fetal systems [19]. After birth, breastfed infants can be exposed to mycotoxins through contaminated breast milk [20]. In the first years of life, hazardous exposure can also occur when infants consume mycotoxin-contaminated infant formulas, fruit-based products, and, particularly, cereal-based baby foods [21,22][21][22].
An additional problem in assessing the effect of mycotoxins exposure effect on children’s health is the nonspecific nature of signs and symptoms attributable to the toxic properties of mycotoxins and the difficulty in considering them in the differential diagnosis of many conditions [23,24][23][24]. Mild forms of mycotoxicosis comprise rash, conjunctivitis, mouth ulcers, epistaxis, apnea, cough, wheezing, nausea, and vomiting, while severe forms include pulmonary hemorrhage, recurrent apnea, “pneumonia”, and bone marrow failure [23].

2. Human Biomonitoring and Health Risks

Assessing the exposure of pregnant women and children to mycotoxins can be carried out through human biomonitoring by direct measurements of biomarkers in biological samples (internal exposure) and determining the presence of mycotoxin levels in foods (external exposure) [25,26][25][26]. Assessing the presence of mycotoxins and concentration of their metabolites in human samples, such as urine, serum, plasma, and breast milk samples [27[27][28],28], aggregates exposure from different sources and by different exposure routes. Hence, human biomonitoring data provides a more accurate estimation of the body burden and can improve risk assessment [29]. In turn, age-stratified human biomonitoring data may be a useful tool for identifying environmental agents, such as mycotoxins, that may be of concern for vulnerable populations, such as children and pregnant women. Combined with additional efforts to identify potential sources of exposure, human biomonitoring could assist policymakers in prioritizing their actions to reduce mycotoxin exposure [30].
The analysis of biomarkers of exposure in biological matrices has become a common method in determining exposure to different mycotoxins [27,28,31][27][28][31]. Urine analysis presents some advantages because sampling is non-invasive and collection is easy; however, it reflects day-to-day variations in mycotoxin intake and, therefore, samples should be taken at different times over a 24 h period. Serum and plasma matrices have the advantage of requiring less sensitive methods because they contain higher levels of compounds. In addition, while urinary excretion normally indicates recent mycotoxin intake, plasma and serum measurements indicate long-term exposure. However, they are limited in that they require invasive collection methods and medical professionals. Breast milk can be used to monitor lactating women; nonetheless, it is an excellent source of information for exposure to breastfed infants [28]. In mothers and children, serum/plasma AF-albumin (AF-alb) and aflatoxin B1-lysine (AFB1-lys) adducts and breast milk AFM1 were also used as biomarkers for AF exposure [10]. There is a variety of selective and sensitive techniques for mycotoxin biomarker determination. High-performance liquid chromatography is widespread because of its superior performance and reliability compared to thin-layer chromatography with a high quality of separation and low limits of detection. Multiple detection systems may be coupled with chromatography, including fluorescence, ultra-violet, diode-array, electrochemical, mass spectrometry, and tandem mass spectrometry, which has advanced in the last years to the status of the reference in the field of mycotoxin analysis [27,32,33][27][32][33]. Biomarker analyses may, however, not be a perfect method for assessing mycotoxin exposure, as blood levels depend on some important factors, such as the narrow detection window for most toxins and their bioavailability in biologic fluids [34].

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