Why and how is the developing fetus vulnerable to toxic chemical exposures?

By Susan F. Katz, MD

This essay is in response to: How is the developing fetus vulnerable to toxic chemical exposures, and how can our regulatory system more effectively protect our health in the prenatal period?

In avoiding exposures to toxicants in the developing fetus, I believe our goal should be to be proactive and preventive. We should take into account all three trimesters as well as periods of continuing neonatal development into infancy and early childhood. We should not have to be reactive to widespread damage found years after a toxicant has entered the environment. This is especially true for those toxicants which are persistent and bioaccumulative in reproductive aged females. These stored toxicants are released during pregnancy along with the fat stores required to nourish and supply energy to the fetus.

There are a number of long recognized important reasons why children in all stages of development are more susceptible to the toxic effects of environmental chemicals of many classes. These include mechanisms that increase both exposure and risk: rapid cell reproduction rates; sensitive periods of development for different organ systems; greater surface areas in skin, lungs, and intestinal mucosa per unit of body weight (so that more toxicants are absorbed per unit of body weight); immature liver and kidney enzyme systems to metabolize, conjugate, and eliminate toxicants; undeveloped blood brain barrier so that transport into the brain occurs in the fetus and child, but not in the adult brain. Additionally, behaviors of the infant and toddler -- such as being close to the ground where concentrations of toxicants in air and dust are greater, hand to mouth behaviors, and drinking more fluids and eating more food per unit of body weight -- all lead to greater exposure and therefore greater risk of damage from a variety of toxicants. And of course a longer “shelf life” gives more time to develop diseases. This is suggested by recent epigenetic explanations of prenatal exposure as a possible mechanism for determining later adult disease patterns.

All of these mechanisms of increased exposure and absorption are made worse by socioeconomic conditions which include poverty and poor nutrition. If the nutritional status of the infant is compromised and there is inadequate intake of protein, calcium, and iron, for example, the absorption of toxic substances such as lead is increased. Secondly, a high fat diet increases exposures to toxicants which are absorbed by and with fat and stored there.

Can we estimate how much of any given toxicant is found in the bodies of our children? Biomonitoring studies now make it possible to start to quantify the exposure. However, national epidemiological studies such as NHANES from the CDC have data only for children over 6. Cord blood monitoring could give data on a large scale, as this is the least invasive method of measuring what exposures actually have been during early development.

Prenatal exposures to some toxicants have been firmly linked to known negative reproductive effects. Well-documented examples include the relationship between sulfur dioxide in air and cardiac birth defects, and arsenic exposures associated with severe congenital malformations. Other pollutants have been measured in air samples at levels associated with adverse reproductive effects such as premature birth and growth retardation with decreases in birth length, weight, and head circumference. And an increasing body of evidence indicates that there are measurable neurodevelopmental and cognitive effects of early exposures to environmental toxicants.

New human epidemiological studies on prenatal exposures to estrogenic endocrine disruptors are showing associations with early puberty in girls, feminization of male children, and decreases in fertility of both men and women later in life. Exposures to some pesticides, some phthalates, BPA, and perfluorochemicals are being shown to contribute to male testicular dysgenesis syndrome, including increasing birth defects such as undescended testicles and hypospadias, and, later in life, poor semen quality, decreased fertility, and testicular cancer.

Other endocrine disrupting toxicants such as lead, mercury, some phthalates, triclosan, PCBs, and PBDEs are associated with disruption of thyroid hormones in epidemiological studies. In children, of course, thyroid hormone is truly critical to normal development of all kinds.

These are all areas in which research has begun to reveal serious problems for the developing human in a polluted environment.

References which have informed this essay

Landrigan PJ, Goldman LR. 2011. Children's vulnerability to toxic chemicals: a challenge and opportunity to strengthen health and environmental policy. Health Aff (Millwood) 30(5): 842-850.

Sexton K, Ryan AD, Adgate JL, Barr DB, Needham LL. 2011. Biomarker measurements of concurrent exposure to multiple environmental chemicals and chemical classes in children. J Toxicol Environ Health A 74(14): 927-942.

Woodruff TJ, Carlson A, Schwartz JM, Giudice LC. 2008. Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: executive summary.Fertil Steril 89(2): 281-300

Parker JD,  Rich DQ, Glinianaia SV, Leem JH, Wartenberg D, Bell ML, et al. 2011. The International Collaboration on Air Pollution and Pregnancy Outcomes: initial results.Environ Health Perspect 119(7): 1023-102

Wigle DT, Arbuckle TE, Turner MC, Berube A, Yang Q, Liu S, et al. 2008. Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants. J Toxicol Environ Health B Crit Rev 11(5-6): 373-517.

Ahern MM, Hendryx M, Conley J, Fedorko E, Ducatman A, Zullig KJ. 2011. The association between mountaintop mining and birth defects among live births in central Appalachia, 1996-2003. Environ Res. 111(6): 838-846.

Gilboa S,  Mendola P, Olshan AF, Langlois PH, Savitz DA, Loomis D, Herring AH,Fixler DE. 2005. Relation between ambient air quality and selected birth defects, seven county study, Texas, 1997-2000.  Am J Epidemiol 162(3):238-52

Vrijheid M, Martinez D, Manzanares S, Dadvand P, Schembari A, Rankin J, et al. 2011. Ambient air pollution and risk of congenital anomalies: a systematic review and meta-analysis. Environ Health Perspect 119(5): 598-606.

Miranda ML, Maxson P, Edwards S. 2009. Environmental contributions to disparities in pregnancy outcomes. Epidemiol Rev 31: 67-83

Shah PS, Balkhair T. 2011. Air pollution and birth outcomes: a systematic review.Environ Int 37(2): 498-516

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