- Environmental toxins and fetal development
It has long been known that the fetus can be sensitive to impacts from adverse environmental
exposure s. Fetal development can be affected by exposures that occur to either parent prior to conception and to the mother post conception.Fetal development
Historically, it was recognized that certain
infection s orpoison s that were harmful to thepregnant woman often were as harmful, or more harmful, to the fetus. Infectious syndromes such ascongenital rubella syndrome andcongenital syphilis were examples. In the last century evidence emerged that certain environmental exposures that were not obviously harmful to the mother could cause serious harm to the fetus. Substances that causedbirth defect s and other adverse effects to the fetus, in the absence of recognized toxicity to mothers, were: genital abnormalities andvaginal cancer occurring among girls born to mothers given the estrogenic hormonediethylstilbestrol during pregnancy;phocomelia (failure of growth of limb buds) to babies born to mothers who tookthalidomide to control nausea during pregnancy; andMinamata disease , an epidemic of babies born with severe mental retardation and deformities due tomercury poisoning caused by mothers eatingmethylmercury contaminated fish from Minimata Bay inJapan . More recently, maternaltobacco smoking and evenenvironmental tobacco smoke , modest consumption ofethanol during pregnancy, and low levels of exposure tolead and mercury have been found to be have adverse impacts on fetal growth and development. The healthyplacenta does form a barrier for mostpathogens and for certainxenobiotic substances. However, it is by design an imperfect barrier since it must transport substances required for growth and development, such as nutrients andimmunoglobulins . Placental transport can be by passivediffusion for smallermolecule s that arelipid soluble or byactive transport for substances that are larger and/or electricallycharged . Some toxic chemicals may be actively transported. For example, it is believed thatlead is transported using mechanisms designed for transport ofiron ,calcium and possibly other essential elements such aszinc . Thedose of a substance received by the fetus is determined by the amount of the substance transported across the placenta as well as the rate ofmetabolism andelimination of the substance. The fetus has immaturemetabolism and is not able to detoxify substances very efficiently; the only routes ofexcretion is via diffusion or active transport back to the maternal circulation or elimination into the amniotic fluid.The timing and duration of exposure are critical. The level of response to a given dose may change dramatically depending on the stage of development at which a fetus is exposed. To identify potential hazards for fetal development requires a basis of scientific information. In 2004, Brent proposed a set of criteria for identifying causes of
congenital malformations that also are applicable to developmental toxicity generally. Those criteria are:
* There are well conductedepidemiology studies consistently show a relationship between particular effects and exposure to the substance to humans.
* Trends in data over time support a relationship between changing levels of exposure to a substance and the specific effect.
* Animal studies give evidence that the fetus is susceptible and provide biological information that is supportive of the human studies and specifically:
** (1) evidence for adose response ;
** (2) the embryonic stage of exposure is critical to whether the developmental effect will be produced;
** (3) specificity between the substance and the effect to be produced; and
** (4) lack of effects other than those produced by a specific substance (that are suggestive of a different mechanism).ref|Brent2004Environmental toxins
Bioaccumulation andpersistence are important aspects to consider since such substances are more likely to be present over several developmental stages than substances that are quickly eliminated. Such substances, known aspersistent organic pollutant s (POPs), include a number of chemicals that are known to have adverse effects on fetal development given the level and timing of exposure:polychlorinated biphenyl s (PCBs),polychlorinated dibenzo-p-dioxins and polychlorinateddibenzofuran s andorganochlorine insecticide s such asDDT are examples of such compounds that can be toxic to the fetus at high enough doses. Others, such aslead andmethylmercury are persistent but not bioaccumulative. (Later, such chemicals continue to be passed from mother to baby viabreast milk .ref|bsk1994A number of environmental toxins known to have adverse effects on fetal development are
endocrine disruptor s. Processes involved with differentiation and growth of embryonic and fetal cells are under the tight control of a myriad of messaging systems, some of which involve hormones. In particular, chemicals that mimic or otherwise disrupt the normal response toestrogen ,androgen , orthyroid hormone have been particularly of concern during fetal development.Environmental
carcinogens also are of concern during this time. Research has indicated that in utero exposure to carcinogens may confer much higher risks than later in life. This may be due to the rapid growth and differentiation of cells during this time, with, perhaps, less ability to repair the damage caused by carcinogens or to mount an effectiveimmune response.References
Footnotes
# Brent, R.L., Environmental causes of human congenital malformations: the pediatrician's role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics, 2004. 113(4 Suppl): p. 957-68.
# "Children's Health".Chemical & Engineering News ,April 7 ,2003 , pp. 23-26.General
# Buelke-Sam, Judy and Kimmel, Carol A., eds. Developmental Toxicology. (1994). 2nd ed. New York: Raven Press.
# Chudley, Persaud & Skalko. Basic Concepts in Teratology. (1985) New York: Alan R. Liss, Inc.
# Schardein, James L., ed. Chemically Induced Birth Defects. (2000). 3rd ed.
# Steingraber, Sandra. (2001). Having Faith. Cambridge, MA: Perseus Publishing.
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