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will show themselves during the early years of life. There is often a threshold of organ function below which symptoms occur and it may not be until the influences of natural physical decline in adulthood and older age are added to early injury that disease will become obvious. There are three major periods of vulnerability to the adverse effects of air pollution during this critical period of early childhood development. Pregnant women are susceptible to the effects of air pollution. The health of the developing fetus is intricately dependent on the health and wellbeing of its mother and on the function of the placenta. Illnesses or exposure of the mother to harmful substances, such as tobacco smoke, can result in slowing of fetal growth. This can affect the growth of different organs and, if growth is hampered at a critical time of development, can lead to permanent damage. This is an example of indirect harm due to air pollution. However, direct harm to the fetus may also occur owing to transfer of toxic substances from the mother's blood across the placenta. Although the placenta has a barrier function to filter out substances harmful to the fetus, several pollutants, such as heavy metals and fine particles (PM 2.5 and smaller), are able to cross the placental barrier 1 and have the potential to cause injury to the fetus and its developing organs. The developing fetus is susceptible to the effects of air pollution. From the earliest stages of development, the building block of life, DNA, is susceptible to changes arising from exposure to air pollution. This can be in the form of physical changes to the DNA structure or influences on how genes function. Even modifications of mothers' DNA before conception could influence fetal development. The fetus is also undergoing a remarkable and coordinated process of organ development, which follows a time-dependent course. As discussed above, even seemingly trivial interference during critical periods can irrevocably harm organs and tissues (the fetal brain and nervous system are exquisitely sensitive to these effects) or change their developmental trajectory so that their function is permanently impaired. Infants are susceptible to the effects of air pollution. Even after birth, there is considerable development and maturation of organs that makes them vulnerable to harmful effects of pollution. Infants are relatively immobile and dependent on their parents to protect them or move them from sources of pollution, yet their main mode of outdoor transport seems designed to put them at precisely the level of motor vehicle exhaust emissions (Fig 8). Infants have a relatively high metabolic rate, so they breathe a greater volume of air per minute than an adult relative to their size. This is a double jeopardy: they get exposed to relatively higher doses of toxic pollutants, as well as being more vulnerable to their harmful effects. 3.3 How does air pollution affect human development? 3.3.1 What does air pollution do to pregnancy outcomes? The placenta contains a myriad of blood vessels from both the fetal and the maternal circulations, which grow very rapidly in early pregnancy. There are several possible mechanisms through which air pollution can harm placental and hence fetal development, although it is unclear which of these is the most important. It is known that air pollution harms blood vessels in later life, giving rise to heart attacks and strokes. It would not be unreasonable, then, to expect some effect of air pollution on the placental blood vessels, but whether the time course of 9 months is sufficient for any effects to 3 In the beginning: protecting our future generations © Royal College of Physicians 2016 39