Pre-and postnatal exposure to environmental toxicants and child health with main focus on growth/obesity

According to a recent WHO/UN report, pollutants with hormone-causing effects are a major threat to human health. We are exposed to an ever-increasing number of such chemicals. One of the many potential adverse health effects is obesity. In this project we found strong evidence for an effect on weight from the levels children in Norway are exposed to. The most important result was observed in an European collaboration in which 26,000 mother-child couples participated. Here we observed that the children of mothers who ate > 3 fish meals a week had an increased risk of being overweight later (Stratakis et al. JAMA Pediatr 2016). Highly educated mothers consumed most fish, and they are expected to have less overweight children, not more, due to in general having a healthy lifestyle. Therefore, the results were surprising. It is likely due to environmental toxins in the fish which may outweigh the positive aspects of fish when the intake is large. Fish contains more environmental toxins than other foods, but there is also great variation between different fish species and choosing less polluted species is likely beneficial. We also studied specific toxins the child was exposed to in the womb, and during breastfeeding, and later weight. We found that various environmental toxins can affect weight, and both increase and decrease it. Both are equally negative as it means that they affect the fine-tuned metabolism in the human body. In the following we mention what we found for some specific environmental toxins. Dioxin and furans are very toxic substances, which are known to increase the risk of cancer, but which can also act as hormone mimics according to new research. We confirmed this. There was a 54% increased risk of obesity at the age of 7 in daughters of highly exposed mothers compared with daughters of low-exposed mothers (Iszatt N. Environ Int. 2016). Interestingly, we found no effects in boys. It is expected that hormone-mimicking chemicals may have different effects in girls and boys. The chemist who invented DDT received the Nobel Prize for his work as it so effectively eradicated all types of pests. We now know that it also kills birds and harms humans and it has been banned for more than 40 years. Nevertheless, the degradation product, DDE, is still found in high levels in breast milk from all Norwegian mothers. In a large study with data from 6 European countries, we observed that DDE was associated with rapid infant growth, a risk factor for later obesity. In the same collaboration, we found that PCB153 had the opposite effect (Iszatt et al. EHP 2015). Reduced growth rate early in life is actually also a risk factor for later obesity. In another multicenter study, higher PCB and DDE levels were associated with lower thyroid stimulating hormones in neonates. Thyroid hormones play a role in metabolism and this may be an underlying mechanism for altered growth (de Cock et al. Pediatr Res 2017). We are developing a model that makes it possible to calculate the child's exposure to environmental toxins through different age stages (fetal life, infant period, toddler period, puberty) based on a few measurements. All results are based on the Norwegian breast milk study HUMIS which includes 2606 mothers and children.

Prosjektet viser at selv om konsentrasjonene av mange av de "gamle " miljøgiftene er gått kraftig ned i morsmelk, ser man fortsatt at barn som er eksponert i øverste kvartil har økt risiko for raskt vekst og senere overvekt. Dette er viktig kunnskap for regulatoriske myndigheter da det viser behov for å sette tolerable grenser for flere av de miljøgiftene vi har undersøkt enda lavere, og iverksette tiltak for å redusere nivåene i miljøet ytterligere. Videre viser det behov for oppdaterte kostråd til alle fertile kvinner (fra barndom av) i forhold til hvilke fiskearter man bør unngå for å holde nivåene i kroppen lavest mulig til man har fått de barna man vil ha.

Overall, there is lack limited knowledge of the health effects of exposure to environmental contaminants in children. The health outcome of focus in this current application is overweight and apart from being a timely topic of large public health importance, another reason for focusing on obesity is that it will compliment on an ongoing multidisciplinary EU project (OBELIX). Support for effects of persistent contaminants on obesity, diabetes and metabolic syndrome has been reported, but more knowledge cl early needed. Specifically, studies addressing the effect of postnatal exposure on child health are needed and in this context models that can be used to assess postnatal exposure are needed. Furthermore, studies on organotins are especially called for, since experimental studies have shown impressive obesogenic properties of organotins in experimental studies. This proposal is based on the Norwegian Human Milk Study (HUMIS) which was established for the purpose of assessing exposure levels to persistent toxicants and study potential health effects of such contaminants. Extensive chemical analyses have already been performed in a subset of children. An extensive collaboration with has been set up as part of this project in order to measure contaminants of interest. Collaboration within other networks of cohorts, and other EU projects, such as OBELIX, ENRIECO and CHICOS has been established. This proposal will provide novel and much needed knowledge on exposure levels to organotins and PFC contaminants and the effect of these and other persistent contaminants on growth and obesity. Furthermore, models for assessing postnatal exposure will be completed and validated. The investments we apply for in this grant, should however be seen as in investment on a much broader scale, since it will strengthen the HUMIS cohort and thereby contribute to future increased knowledge on multiple health outcomes as well.